RESUMEN
PURPOSE: Cancer-related fatigue (CRF) is a debilitating symptom experienced by many cancer patients. Although guidelines provide evidence-based recommendations for screening, assessing, and managing CRF, there is limited evidence of their implementation in practice. This study aimed to explore patients', healthcare providers' (HCPs), community support providers' (CSPs) experiences and opinions on CRF guidelines and the underlying causes of CRF treatment gaps following the Knowledge-to-Action model. METHODS: A total of 62 participants were recruited-16 patients, 32 HCPs, and 14 CSPs-for a total of 9 focus groups and 4 individual interviews. Sessions were recorded and transcribed verbatim. Transcripts were analyzed using thematic analysis. RESULTS: There were gaps in the application of CRF guidelines and patient dissatisfaction with care. Two underlying mechanisms may contribute to these gaps. First, professionals' lack of knowledge and resources paired with systemic obstacles created difficult conditions to adequately address CRF-A Perfect Storm. Further, patient-provider communication gaps lead to patients feeling discouraged to report issues to their healthcare teams and turning to community services for help-A Breakdown in Communication. CONCLUSIONS: There is little indication that CRF guidelines are routinely implemented in clinical practice. This study provides insights from various perspectives to aid understanding of the critical issues that require consideration to increase implementation of CRF guidelines by HCPs. As patients are currently dissatisfied with CRF-related care, implementation of CRF guidelines is needed.
Asunto(s)
Fatiga/etiología , Neoplasias/complicaciones , Brechas de la Práctica Profesional/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Comunicación , Femenino , Guías como Asunto , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Cryptosporidium sp. are common intracellular parasites responsible of severe diarrhea in T-cell-immunocompromised patients. We report the first case of a woman who contracted cryptosporidiosis after treatment with fingolimod, a drug labeled for multiple sclerosis and responsible for marked lymphopenia. CASE PRESENTATION: A 60-year-old woman was admitted for abdominal pain diarrhea and fever. The patient suffered from multiple sclerosis and had been treated with fingolimod from august 2017 to september 2018 time of occurrence of the first digestive symptoms. Stool culture was negative but parasitological examination was positive for Cryptosporidium sp. Blood biological examination profound lymphopenia of 240/mm3 [17 CD4/mm3 (7%) and 32 CD8/mm3 (14%)]. Fingolimod was stopped, and the patient was put on nitazoxanide 500 mg bid for 7 days. The diarrhea resolved and no relapse was observed. Six other cases were found in the Pharmacovigilance database. CONCLUSION: Physicians should be aware of this association and screen for Cryptosporidium in cases of diarrhea in patients treated with fingolimod. Patients should be aware of this risk and advise to take appropriate measures to avoid such contamination.
Asunto(s)
Criptosporidiosis/tratamiento farmacológico , Diarrea/parasitología , Clorhidrato de Fingolimod/efectos adversos , Dolor Abdominal/parasitología , Animales , Antiparasitarios/uso terapéutico , Criptosporidiosis/parasitología , Diarrea/etiología , Heces/parasitología , Femenino , Fiebre/parasitología , Clorhidrato de Fingolimod/uso terapéutico , Humanos , Huésped Inmunocomprometido , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Nitrocompuestos , Farmacovigilancia , Tiazoles/uso terapéuticoRESUMEN
Terrestrial ecosystems are exposed to various kinds of pollutants, including radionuclides. The honeybee, Apis mellifera, is commonly used in ecotoxicology as a model species for evaluating the effects of pollutants. In the present study, honeybees were irradiated right after birth for 14 days with gamma rays at dose rates ranging between 4.38â¯×â¯10-3 and 588â¯mGy/d. Biological tissues (head, intestine and abdomen) were sampled at D3, D10 and D14. Ten different physiological markers involved in nervous (acetylcholinesterase (AChE)), antioxidative (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST)), immune system (phenoloxidase (PO)) and metabolism (carboxylesterases (CaEs) and alkaline phosphatase (ALP)) were measured. Univariate analyses were conducted to determine whether each individual biomarker response was positively or negatively correlated with the dose rate. Then, multivariate analyses were applied to investigate the relationships between all the biomarker responses. Although no mortality occurred during the experiment, several biomarkers varied significantly in relation to the dose rate. Globally, the biomarkers of antioxidant and immune systems decreased as the dose rate increased. Reversible effects on the indicator of the neural system were found. Concerning indicators of metabolism (carboxylesterases), variations occurred but no clear pattern was found. Taken altogether, these results help better understand the effects of ionizing radiation on bees by identifying relevant physiological markers of effects. These results could improve the assessment of the environmental risk due to ionizing radiation in terrestrial ecosystems.
Asunto(s)
Abejas/efectos de la radiación , Rayos gamma , Contaminantes Radiactivos/toxicidad , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/metabolismo , Abejas/metabolismo , Biomarcadores/metabolismo , Hidrolasas de Éster Carboxílico/metabolismo , Catalasa/metabolismo , Ecotoxicología/métodos , Glutatión Peroxidasa/metabolismo , Glutatión Transferasa/metabolismo , Monofenol Monooxigenasa/metabolismo , Análisis Multivariante , Contaminantes Radiactivos/análisis , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.
Asunto(s)
Asesoramiento Genético/psicología , Predisposición Genética a la Enfermedad/psicología , Pruebas Genéticas/métodos , Neoplasias/psicología , Adulto , Ansiedad/psicología , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/genética , Neoplasias/prevención & control , EspañaRESUMEN
PURPOSE: In this study, we examined the effects of a 30-week community-based exercise program on cancer-related fatigue, quality of life, and other health-related outcomes in a sample of adults with mixed cancer diagnoses. METHODS: This prospective cohort study looked at outcomes for participants involved in the Wellspring Cancer Exercise Program in southern Ontario. The program consisted of an initial phase of two supervised sessions weekly for 10 weeks and a transition phase of one supervised session weekly for the subsequent 20 weeks. Outcomes were measured at baseline and every 10 weeks throughout the intervention, as well as at 16 weeks after program completion. RESULTS: During a period of 13 months, 229 of the 355 cancer survivors who enrolled in the exercise program consented to participate in the study. Participants attended 71% of the supervised exercise sessions in the initial phase and 49% in the transition phase. From baseline to the end of the initial phase, significant improvements in cancer-related fatigue, 6-minute walk test, social well-being, systolic blood pressure, balance, and physical activity volume were observed. During the transition phase, health-related quality of life and emotional well-being improved significantly. CONCLUSIONS: The Wellspring Cancer Exercise Program is associated with clinically meaningful improvements in cancer-related fatigue and functional aerobic capacity. Several other aspects of well-being in cancer survivors also improved for participants in the program. Community-based cancer exercise programs such as the Wellspring Cancer Exercise Program can improve well-being for cancer survivors and can provide an effective option that enhances sustainability and accessibility to exercise services for this population.
RESUMEN
Breast cancer (BC) is the most frequent cancer among women in Morocco. However, the role of the most prevalent BC-predisposing genes, BRCA1 and BRCA2, has been largely unexplored. To help define the role of BRCA1 in BC in Morocco, we characterized the first potential BRCA1 founder mutation in this population. Genetic testing of BRCA1 and BRCA2 in BC high-risk families identified mutation BRCA1 c.5309G>T, p.(Gly1770Val) or G1770V in five independent families from Morocco, suggesting a founder effect. To confirm this hypothesis, haplotype construction was performed using seven intragenic and flanking BRCA1 microsatellite markers. Clinical data were also compiled. Clinical data from carriers of mutation G1770V correspond to data from carriers of BRCA1 pathogenic mutations. Microsatellite analysis showed a common haplotype for the five families in a region comprising 1.54 Mb, confirming G1770V as the first specific founder BRCA1 mutation in the Moroccan population. Our findings contribute to a better understanding of BC genetics in the Moroccan population. Nevertheless, comprehensive studies of mutation G1770V in large series of BC patients from Morocco are needed to assess the real prevalence of this mutation and to improve genetic testing and risk assessment in this population.
Asunto(s)
Proteína BRCA1/genética , Efecto Fundador , Mutación , Adulto , Proteína BRCA1/química , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Repeticiones de Microsatélite , Persona de Mediana Edad , Marruecos , LinajeRESUMEN
BACKGROUND: Cryptosporidium spp. is a ubiquitous parasite affecting humans as well as domestic and wild vertebrates, causing diarrhea in both immunocompetent and immunocompromised hosts worldwide. Its transmission occurs primarily by the fecal-oral route. In humans, C. parvum and C. hominis are the most prevalent species, whereas immunocompetent and immunocompromised individuals can also be infected by other zoonotic species. Renal transplant patients are prone to develop cryptosporidiosis, which can induce severe and life-threatening diarrhea. CASE PRESENTATION: We report here a series of nearly concomitant cases of acute symptomatic cryptosporidiosis in three renal transplant patients attending the Strasbourg University Hospital Nephrology Unit. The clinical presentation was persistent diarrhea and acute renal failure. The diagnosis was confirmed by microscopic stool examination using a modified Ziehl-Neelsen staining method and species identification by molecular tools. All patients were treated with nitazoxanide and recovered from diarrhea after 14 days of therapy. CONCLUSION: Genotypic species identification was not consistent with an epidemic context, thus underlining the need for genotyping to monitor at risk patients.
Asunto(s)
Infección Hospitalaria/parasitología , Criptosporidiosis/transmisión , Cryptosporidium/patogenicidad , Trasplante de Riñón , Lesión Renal Aguda/etiología , Lesión Renal Aguda/parasitología , Adulto , Animales , Coccidiostáticos/uso terapéutico , Criptosporidiosis/complicaciones , Criptosporidiosis/tratamiento farmacológico , Cryptosporidium/genética , Diarrea/etiología , Diarrea/parasitología , Heces/parasitología , Femenino , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Nitrocompuestos , Tiazoles/uso terapéuticoRESUMEN
BACKGROUND: To improve the prevention, treatment and risk prediction of cardiovascular diseases, genetic markers and gene-diet interactions are currently being investigated. The Montreal Heart Institute (MHI) Biobank is suitable for such studies because of its large sample size (currently, n = 17 000), the availability of biospecimens, and the collection of data on dietary intakes of saturated (SFAs) and n-3 and n-6 polyunsaturated (PUFAs) fatty acids estimated from a 14-item food frequency questionnaire (FFQ). We tested the validity of the FFQ by correlating dietary intakes of these fatty acids with their red blood cell (RBC) content in MHI Biobank participants. METHODS: Seventy-five men and 75 women were selected from the Biobank. We successfully obtained RBC fatty acids for 142 subjects using gas chromatography coupled to mass spectrometry. Spearman correlation coefficients were used to test whether SFA scores and daily intakes (g day(-1)) of n-3 and n-6 PUFAs correlate with their RBC content. RESULTS: Based on covariate-adjusted analyses, intakes of n-3 PUFAs from vegetable sources were significantly correlated with RBC α-linolenic acid levels (ρ = 0.23, P = 0.007), whereas n-3 PUFA intakes from marine sources correlated significantly with RBC eicosapentaenoic acid (ρ = 0.29, P = 0.0008) and docosahexaenoic acid (ρ = 0.41, P = 9.2 × 10(-7)) levels. Intakes of n-6 PUFAs from vegetable sources correlated with RBC linoleic acid (ρ = 0.18, P = 0.04). SFA scores were not correlated with RBC total SFAs. CONCLUSIONS: The MHI Biobank 14-item FFQ can appropriately estimate daily intakes of n-3 PUFAs from vegetable and marine sources, as well as vegetable n-6 PUFAs, which enables the possibility of using these data in future studies.
Asunto(s)
Bancos de Muestras Biológicas/estadística & datos numéricos , Dieta/métodos , Eritrocitos/metabolismo , Ácidos Grasos/administración & dosificación , Conducta Alimentaria , Encuestas y Cuestionarios , Canadá , Dieta/estadística & datos numéricos , Ácido Eicosapentaenoico/sangre , Ácidos Grasos/sangre , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Ácido alfa-Linolénico/sangreRESUMEN
We report a case of a 73 year-old man admitted for acute mesenteric ischaemia. Eight years before, he had a first mesenteric ischaemic event treated by left colectomy and angioplasty of both main coeliac artery (MCA) and superior mesenteric artery (SMA); the patient was discharged on lifelong clopidogrel and aspirin. One month before his admission for the index event, he had a major haematuria; clopidogrel was stopped first, then aspirin because of recurrent haematuria. Five days after withdrawal of both antiplatelet drugs, the patient presented with acute mesenteric ischaemia. Urgent aortography showed in-stent occlusion of SMA and in-stent restenosis of MCA; we performed ad hoc thrombus aspiration of SMA and balloon angioplasty of MCA. The patient was discharged seven days after, without complications. This case shows that very late stent thrombosis in digestive artery can occur in the setting of antiplatelet arrest and urgent endovascular intervention constitutes a seductive alternative for surgery when performed early after symptoms onset.
Asunto(s)
Angioplastia de Balón/métodos , Isquemia Mesentérica/terapia , Inhibidores de Agregación Plaquetaria/efectos adversos , Falla de Prótesis , Stents/efectos adversos , Anciano , Angiografía/métodos , Estudios de Seguimiento , Humanos , Masculino , Isquemia Mesentérica/diagnóstico por imagen , Metales , Inhibidores de Agregación Plaquetaria/administración & dosificación , Recurrencia , Retratamiento/métodos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Privación de TratamientoRESUMEN
Germline deletions at the 3'-end of EPCAM have been involved in the etiology of Lynch syndrome (LS). The aim of this study was to characterize at the molecular level Spanish families harboring EPCAM deletions. Non-commercial multiplex ligation-dependent probe amplification (MLPA) probes and long-range polymerase chain reaction (PCR) amplification were used to characterize each deletion. Haplotyping was performed by analyzing eight microsatellite markers and five MSH2single nucleotide polymorphisms (SNPs). Methylation of MSH2 was analyzed by methylation specific-MLPA. Tumors diagnosed in seven Spanish families harboring EPCAM deletions were almost exclusively colorectal. Mosaicism in MSH2 methylation was observed in EPCAM deletion carrier samples, being average methylation levels higher in normal colon and colorectal tumors (27.6% and 31.1%), than in lymphocytes and oral mucosa (1.1% and 0.7%). Three families shared the deletion c.858 + 2568_*4596del, with a common haplotype comprising 9.9 Mb. In two families the novel EPCAM deletion c.858 + 2488_*7469del was identified. This study provides knowledge on the clinical and molecular characteristics of mosaic MSH2 epimutations. The identification of an EPCAM founder mutation has useful implications for the molecular diagnosis of LS in Spain.
Asunto(s)
Antígenos de Neoplasias/genética , Moléculas de Adhesión Celular/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Efecto Fundador , Eliminación de Gen , Adulto , Colestasis , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Metilación de ADN , Reparación de la Incompatibilidad de ADN , Molécula de Adhesión Celular Epitelial , Femenino , Sitios Genéticos , Mutación de Línea Germinal , Haplotipos , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Proteína 2 Homóloga a MutS/genética , Neumonía , Regiones Promotoras Genéticas , España , Adulto JovenRESUMEN
Forest floor vegetation is an important component of forest biodiversity, and numerous studies have shown that N input alters the vegetation. In some cases, however, the effects of experimental N addition have been small or absent. Two alternative hypotheses have been suggested: (a) competition from the tree layer confounds the response to N, or (b) N response in areas with high background deposition is limited by N saturation. Neither of these hypotheses has so far been explicitly tested. Here, we compile data on forest floor vegetation from N addition experiments, in which the forest had been clear-cut, along an N deposition gradient ranging from 4 to 16 kg ha(-1) year(-1) in Sweden. We analyzed the effects of N addition and its interaction with N deposition on common species and thereby tested the second hypothesis in an environment without the confounding effects of the tree layer. The results show that the effects of the experimental N addition are significantly influenced by background N deposition: the N addition effects are smaller in areas with high N deposition than in areas with low N deposition, despite the fact that the highest N deposition in this study can be considered moderate from an international perspective. The results are important when assessing the reliability of results from N addition experiments on forest floor vegetation in areas with moderate to high background N deposition. We conclude that the interacting effects of N addition and N deposition need to be included when assessing long-term N sensitivity of plant communities.
Asunto(s)
Ecosistema , Nitrógeno/metabolismo , Fenómenos Fisiológicos de las Plantas , Biodiversidad , Agricultura Forestal , Suecia , ÁrbolesRESUMEN
Aortic dissection is a complex, intramural, and dynamic condition involving multiple mechanisms, hence, difficult to observe. In the present study, a controlled in vitro aortic dissection was performed using tension-inflation tests on notched rabbit aortic segments. The mechanical test was combined with conventional (cCT) and synchrotron (sCT) computed tomography for in situ imaging of the macro- and micro-structural morphological changes of the aortic wall during dissection. We demonstrate that the morphology of the notch and the aorta can be quantified in situ at different steps of the aortic dissection, and that the notch geometry correlates with the critical pressure. The phenomena prior to propagation of the notch are also described, for instance the presence of a bulge at the tip of the notch is identified, deforming the remaining wall. Finally, our method allows us to visualize for the first time the propagation of an aortic dissection in real-time with a resolution that has never previously been reached. STATEMENT OF SIGNIFICANCE: With the present study, we investigated the factors leading to the propagation of aortic dissection by reproducing this mechanical process in notched rabbit aortas. Synchrotron CT provided the first visualisation in real-time of an aortic dissection propagation with a resolution that has never previously been reached. The morphology of the intimal tear and aorta was quantified at different steps of the aortic dissection, demonstrating that the early notch geometry correlates with the critical pressure. This quantification is crucial for the development of better criteria identifying patients at risk. Phenomena prior to tear propagation were also described, such as the presence of a bulge at the tip of the notch, deforming the remaining wall.
Asunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Animales , Conejos , Sincrotrones , Disección Aórtica/diagnóstico por imagen , Aorta/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Imaging across different scales is essential for understanding healthy organ morphology and pathophysiological changes. The macro- and microscale three-dimensional morphology of large samples, including intact human organs, is possible with X-ray microtomography (using laboratory or synchrotron sources). Preparation of large samples for high-resolution imaging, however, is challenging due to limitations such as sample shrinkage, insufficient contrast, movement of the sample and bubble formation during mounting or scanning. Here, we describe the preparation, stabilization, dehydration and mounting of large soft-tissue samples for X-ray microtomography. We detail the protocol applied to whole human organs and hierarchical phase-contrast tomography at the European Synchrotron Radiation Facility, yet it is applicable to a range of biological samples, including complete organisms. The protocol enhances the contrast when using X-ray imaging, while preventing sample motion during the scan, even with different sample orientations. Bubbles trapped during mounting and those formed during scanning (in the case of synchrotron X-ray imaging) are mitigated by multiple degassing steps. The sample preparation is also compatible with magnetic resonance imaging, computed tomography and histological observation. The sample preparation and mounting require 24-36 d for a large organ such as a whole human brain or heart. The preparation time varies depending on the composition, size and fragility of the tissue. Use of the protocol enables scanning of intact organs with a diameter of 150 mm with a local voxel size of 1 µm. The protocol requires users with expertise in handling human or animal organs, laboratory operation and X-ray imaging.
Asunto(s)
Encéfalo , Sincrotrones , Humanos , Animales , Microtomografía por Rayos X/métodos , Encéfalo/diagnóstico por imagen , Imagenología Tridimensional/métodos , Imagen MultimodalRESUMEN
Cardiovascular diseases (CVDs) are a leading cause of death worldwide. Current clinical imaging modalities provide resolution adequate for diagnosis but are unable to provide detail of structural changes in the heart, across length-scales, necessary for understanding underlying pathophysiology of disease. Hierarchical Phase-Contrast Tomography (HiP-CT), using new (4th) generation synchrotron sources, potentially overcomes this limitation, allowing micron resolution imaging of intact adult organs with unprecedented detail. In this proof of principle study (n=2), we show the utility of HiP-CT to image whole adult human hearts ex-vivo: one 'control' without known cardiac disease and one with multiple known cardiopulmonary pathologies. The resulting multiscale imaging was able to demonstrate exemplars of anatomy in each cardiac segment along with novel findings in the cardiac conduction system, from gross (20 um/voxel) to cellular scale (2.2 um/voxel), non-destructively, thereby bridging the gap between macroscopic and microscopic investigations. We propose that the technique represents a significant step in virtual autopsy methods for studying structural heart disease, facilitating research into abnormalities across scales and age-groups. It opens up possibilities for understanding and treating disease; and provides a cardiac 'blueprint' with potential for in-silico simulation, device design, virtual surgical training, and bioengineered heart in the future.
RESUMEN
BACKGROUND: In addition to the mutational status of KRAS, the epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG) might function as bona fide biomarkers of cetuximab (Ctx) sensitivity for most EGFR-driven carcinomas. METHODS: Lentivirus-delivered small hairpin RNAs were employed to specifically reduce AREG or EREG gene expression in wild-type KRAS A431 squamous cell carcinoma cells. Colony-forming assays were used to monitor the impact of AREG and EREG knockdown on Ctx efficacy. Amphiregulin and EREG protein expression levels were assessed by quantitative ELISA in parental A431 cells and in pooled populations of A431 cells adapted to grow in the presence of Ctx. A phosphoproteomic platform was used to measure the relative level of phosphorylation of 42 distinct receptor tyrosine kinases before and after the acquisition of resistance to Ctx. RESULTS: Stable gene silencing of either ligand was found to notably reduce the expression of the other ligand. Parental A431 cells with normal expression levels of AREG/EREG exhibited significantly increased growth inhibition in response to Ctx, compared with derivatives that are engineered to produce minimal AREG/EREG. The parental A431 cells acutely treated with Ctx exhibited reduced basal expression levels of AREG/EREG. Pooled populations of Ctx-resistant A431 cells expressed significantly lower levels of AREG/EREG and were insensitive to the downregulatory effects of Ctx. Phosphoproteomic screen identified a remarkable hyperactivation of FGFR3 in Ctx-resistant A431 cells, which gained sensitivity to the cytotoxic and apoptotic effects of the FGFR3 TK inhibitor PD173074. The A431 parental cells acutely treated with Ctx rapidly activated FGFR3 and their concomitant exposure to Ctx and PD173074 resulted in synergistic apoptosis. CONCLUSION: Cross-suppression of AREG/EREG expression may explain the tight co-expression of AREG and EREG, as well as their tendency to be more highly expressed than other EGFR ligands to determine Ctx efficacy. The positive selection for Ctx-resistant tumour cells exhibiting AREG/EREG cross-suppression may have an important role in the emergence of Ctx resistance. As de-repression of FGFR3 activity rapidly replaces the loss of EGFR-ligand signalling in terms of cell proliferation and survival, combinations of Ctx and FGFR3-targeted drugs may be a valuable strategy to enhance the efficacy of single Ctx while preventing or delaying acquired resistance to Ctx.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Factor de Crecimiento Epidérmico/antagonistas & inhibidores , Receptores ErbB/metabolismo , Glicoproteínas/antagonistas & inhibidores , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Cutáneas/patología , Anfirregulina , Anticuerpos Monoclonales Humanizados , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cetuximab , Familia de Proteínas EGF , Factor de Crecimiento Epidérmico/biosíntesis , Factor de Crecimiento Epidérmico/genética , Epirregulina , Técnicas de Silenciamiento del Gen , Glicoproteínas/biosíntesis , Glicoproteínas/genética , Humanos , Péptidos y Proteínas de Señalización Intercelular/biosíntesis , Péptidos y Proteínas de Señalización Intercelular/genética , Ligandos , Pirimidinas/farmacología , Neoplasias Cutáneas/tratamiento farmacológico , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
The effectiveness of hedgerows as functional corridors in the face of climate warming has been little researched. Here we investigated the effects of warming temperatures on plant performance and population growth of Geum urbanum in forests versus hedgerows in two European temperate regions. Adult individuals were transplanted in three forest-hedgerow pairs in each of two different latitudes, and an experimental warming treatment using open-top chambers was used in a full factorial design. Plant performance was analysed using mixed models and population performance was analysed using Integral Projection Models and elasticity analyses. Temperature increases due to open-top chamber installation were higher in forests than in hedgerows. In forests, the warming treatment had a significant negative effect on the population growth rate of G. urbanum. In contrast, no significant effect of the warming treatment on population dynamics was detected in hedgerows. Overall, the highest population growth rates were found in the forest control sites, which was driven by a higher fecundity rather than a higher survival probability. Effects of warming treatments on G. urbanum population growth rates differed between forests and hedgerows. In forests, warming treatments negatively affected population growth, but not in hedgerows. This could be a consequence of the overall lower warming achieved in hedgerows. We conclude that maintenance of cooler forest microclimates coul, at least temporarily, moderate the species response to climate warming.
Asunto(s)
Geum , Cambio Climático , Bosques , Microclima , Plantas , TemperaturaRESUMEN
Wild bee populations are declining due to human activities, such as land use change, which strongly affect the composition and diversity of available plants and food sources. The chemical composition of food (i.e., nutrition) in turn determines the health, resilience, and fitness of bees. For pollinators, however, the term 'health' is recent and is subject to debate, as is the interaction between nutrition and wild bee health. We define bee health as a multidimensional concept in a novel integrative framework linking bee biological traits (physiology, stoichiometry, and disease) and environmental factors (floral diversity and nutritional landscapes). Linking information on tolerated nutritional niches and health in different bee species will allow us to better predict their distribution and responses to environmental change, and thus support wild pollinator conservation.
Asunto(s)
Biodiversidad , Polinización , Animales , Abejas , Ecosistema , Flores/fisiología , Fenotipo , Plantas , Polinización/fisiologíaRESUMEN
Quercus spp. are one of the most important tree genera in temperate deciduous forests in terms of biodiversity, economic and cultural perspectives. However, natural regeneration of oaks, depending on specific environmental conditions, is still not sufficiently understood. Oak regeneration dynamics are impacted by climate change, but these climate impacts will depend on local forest management and light and temperature conditions. Here, we studied germination, survival and seedling performance (i.e. aboveground biomass, height, root collar diameter and specific leaf area) of four oak species (Q. cerris, Q. ilex, Q. robur and Q. petraea). Acorns were sown across a wide latitudinal gradient, from Italy to Sweden, and across several microclimatic gradients located within and beyond the species' natural ranges. Microclimatic gradients were applied in terms of forest structure, distance to the forest edge and experimental warming. We found strong interactions between species and latitude, as well as between microclimate and latitude or species. The species thus reacted differently to local and regional changes in light and temperature ; in southern regions the temperate Q. robur and Q. petraea performed best in plots with a complex structure, whereas the Mediterranean Q. ilex and Q. cerris performed better in simply structured forests with a reduced microclimatic buffering capacity. The experimental warming treatment only enhanced height and aboveground biomass of Mediterranean species. Our results show that local microclimatic gradients play a key role in the initial stages of oak regeneration; however, one needs to consider the species-specific responses to forest structure and the macroclimatic context.
Asunto(s)
Quercus , Cambio Climático , Bosques , Microclima , Quercus/fisiología , ÁrbolesRESUMEN
Biallelic inactivation of ATM gene causes the rare autosomal recessive disorder Ataxia-telangiectasia (A-T). Female relatives of A-T patients have a two-fold higher risk of developing breast cancer (BC) compared with the general population. ATM mutation carrier identification is laborious and expensive, therefore, a more rapid and directed strategy for ATM mutation profiling is needed. We designed a case-control study to determine the prevalence of 32 known ATM mutations causing A-T in Spanish population in 323 BRCA1/BRCA2 negative hereditary breast cancer (HBC) cases and 625 matched Spanish controls. For the detection of the 32 ATM mutations we used the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technique. We identified one patient carrier of the c.8264_8268delATAAG ATM mutation. This mutation was not found in the 625 controls. These results suggest a low frequency of these 32 A-T causing mutations in the HBC cases in our population. Further case-control studies analyzing the entire coding and flanking sequences of the ATM gene are warranted in Spanish BC patients to know its implication in BC predisposition.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Supresoras de Tumor/genética , Proteínas de la Ataxia Telangiectasia Mutada , Estudios de Casos y Controles , ADN/análisis , ADN/genética , Análisis Mutacional de ADN , Familia , Femenino , Pruebas Genéticas , Humanos , Masculino , Pronóstico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
PURPOSE: Apple pomace is an easily accessible source of bioactive compounds which can be used for various purposes in the food, pharmaceutical and cosmetic industry. Six types of apple pomace extracts were tested to study their health benefits, free radical scavenging and antiproliferative activities. METHODS: The radical scavenging activity was determined by electron spin resonance (ESR) spectroscopy. Antiproliferative action was measured using MTT [3-(4,5-dimethylthiazol- 2-yl)2,5-diphenyl tetrazolium bromide] colorimetric assay in cervix epithelioid carcinoma (HeLa) and colon adenocarcinoma (HT-29) human cancer cell lines. RESULTS: All extracts suppressed the formation of 2,2-diphenyl- 1-picrylhydrazyl (DPPHâ) and hydroxyl-free radical in a dose-dependent manner. In the presence of 12.5 mg/ ml Pinova, Reinders and Nectar pomace extract, the ESR DPPHâ signals vanished. The âOH was completely scavenged in the presence of 45 mg/ml or higher concentration of the investigated extracts. Pinova and Braeburn pomace extracts showed the strongest antiproliferative activity against the investigated human cancer cell lines. Also, HeLa cells were found more sensitive than HT-29 cells to all extracts. CONCLUSION: Although the relationship between radical scavenging activities and phenolic contents or flavonol glycosides (R(2)≥0.80) was high, there were no significant correlations between the total phenolic contents or individual phenolic compounds and the antiproliferative activity.