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1.
Blood ; 135(8): 534-541, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31877211

RESUMO

In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n = 124) or warning (n = 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms.

2.
Cancer Manag Res ; 11: 7991-7996, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692557

RESUMO

Purpose: In our work we sought to define the prevalence rates of cutaneous events during dasatinib therapy in chronic myeloid leukemia (CML) patients and to investigate the clinical and pathological characteristics of these reactions. Patients and methods: In our institution, 67 CML patients were treated with dasatinib. it was given as first line treatment in 26 (39%) and subsequent treatment in 41 (61%) CML patients. Flow cytometry analysis of peripheral blood and cutaneous biopsy was done on all CML patients with dermatological lesions appearing during dasatinib treatment. Results: Among 67 CML patients, 4 (5.9%) showed skin lesions during dasatinib treatment. The cutaneous manifestations were not generalized but mainly located on the back, abdomen, thorax or leg regions. The patients did not show peripheral lymphocytosis at the time when skin lesions appeared. Overall, histological analysis showed that the skin lesions were characterized by a mild perivascular small CD8+ T lymphocytes infiltrate with minimal epidermotropism. Conclusion: The unusual T cytotoxic cutaneous infiltrate demonstrated in our CML cases could be the expression of a dasatinib-promoted lymphocyte expansion. However, the heterogeneity of the dermatologic manifestations reported in our CML patients could also be related to unknown factors specific to each CML patient. Our work highlights the finding that skin lesions may be associated with dasatinib treatment and that they should not be confused with viral or bacterial infections but rather interpreted as the clinical expression of lymphocytosis promoted by this TKI.

3.
Phys Rev Lett ; 123(11): 116102, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31573261

RESUMO

Studying the frictional properties of interfaces with dynamic chemical bonds advances understanding of the mechanism underlying rate and state laws, and offers new pathways for the rational control of frictional response. In this work, we revisit the load dependence of interfacial chemical-bond-induced (ICBI) friction experimentally and find that the velocity dependence of friction can be reversed by changing the normal load. We propose a theoretical model, whose analytical solution allows us to interpret the experimental data on timescales and length scales that are relevant to experimental conditions. Our work provides a promising avenue for exploring the dynamics of ICBI friction.

4.
Ann Hematol ; 98(10): 2329-2338, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31392461

RESUMO

Very elderly (> 75 years) chronic myeloid leukaemia (CML) patients at diagnosis are sometimes treated with different doses of imatinib (IM) based on concomitant diseases and physicians' judgement. However, data on long-term follow-up of these patients are still lacking. To investigate treatment response and outcome, we retrospectively revised an Italian database of 263 very elderly CML patients receiving IM from the time of diagnosis. Median age at diagnosis was 78.5 years and 56% of patients had 2 or 3 comorbidities. A complete haematological and cytogenetic response were achieved in 244 (92.8%) and 184 (69.9%) patients, respectively. In 148 cases (56.2%), a major molecular response was observed, which was deep in 63 cases (24%). A blastic phase occurred in 11 patients (4.2%). After a median follow-up of 45.0 months, 93 patients have died (9 from disease progression) and 104 (39.5%) are still in treatment with IM. Incidence of grades 3-4 haematological and non-haematological toxicity was similar to those reported in younger patients. Five-year event-free survival was 54.5% and 45.2% in patients ≤ 80 years and > 80 years, respectively (p = 0.098). Five years OS was 75.7% and 61.6% in patients ≤80 years and > 80 years, respectively (p = 0.003). These findings show that IM plays an important role in frontline treatment of very elderly CML patients without increased toxicity and any effort to treat these patients with standard doses should be made in order to achieve responses as in younger subjects.


Assuntos
Mesilato de Imatinib/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Mesilato de Imatinib/efeitos adversos , Masculino , Taxa de Sobrevida , Fatores de Tempo
5.
Ann Hematol ; 98(8): 1885-1890, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31044260

RESUMO

There is little information about cardiovascular adverse event (CV-AE) incidence in chronic myeloid leukemia (CML) patients treated with bosutinib in the real-life practice. We identified 54 consecutive CML patients treated with bosutinib, stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 40-month cumulative incidence of CV-AEs was 25.2 ± 8.1%. Patients with the SCORE of high-very high showed a significantly higher incidence of CV-AEs (55 ± 12.9% vs 9 ± 9.5%; p = 0.002). Overall, 9 CV-AEs were reported, with 2 deaths attributed to CV-AE. In conclusion, the SCORE assessment before starting treatment is helpful in identifying CV-AE high-risk patients during bosutinib treatment.


Assuntos
Compostos de Anilina/efeitos adversos , Antineoplásicos/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Infarto do Miocárdio/induzido quimicamente , Nitrilos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/induzido quimicamente , Angina Pectoris/diagnóstico , Angina Pectoris/fisiopatologia , Compostos de Anilina/administração & dosagem , Antineoplásicos/administração & dosagem , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Suscetibilidade a Doenças , Esquema de Medicação , Feminino , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Nitrilos/administração & dosagem , Doenças Vasculares Periféricas/induzido quimicamente , Doenças Vasculares Periféricas/diagnóstico , Doenças Vasculares Periféricas/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Quinolinas/administração & dosagem , Estudos Retrospectivos
6.
J Nutr Sci ; 8: e15, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037218

RESUMO

Coffee consumption is inversely associated with the risk of non-alcoholic fatty liver disease (NAFLD). A gap in the literature still exists concerning the intestinal mechanisms that are involved in the protective effect of coffee consumption towards NAFLD. In this study, twenty-four C57BL/6J mice were divided into three groups each receiving a standard diet, a high-fat diet (HFD) or an HFD plus decaffeinated coffee (HFD+COFFEE) for 12 weeks. Coffee supplementation reduced HFD-induced liver macrovesicular steatosis (P < 0·01) and serum cholesterol (P < 0·001), alanine aminotransferase and glucose (P < 0·05). Accordingly, liver PPAR- α (P < 0·05) and acyl-CoA oxidase-1 (P < 0·05) as well as duodenal ATP-binding cassette (ABC) subfamily A1 (ABCA1) and subfamily G1 (ABCG1) (P < 0·05) mRNA expressions increased with coffee consumption. Compared with HFD animals, HFD+COFFEE mice had more undigested lipids in the caecal content and higher free fatty acid receptor-1 mRNA expression in the duodenum and colon. Furthermore, they showed an up-regulation of duodenal and colonic zonulin-1 (P < 0·05), duodenal claudin (P < 0·05) and duodenal peptide YY (P < 0·05) mRNA as well as a higher abundance of Alcaligenaceae in the faeces (P < 0·05). HFD+COFFEE mice had an energy intake comparable with HFD-fed mice but starting from the eighth intervention week they gained significantly less weight over time. Data altogether showed that coffee supplementation prevented HFD-induced NAFLD in mice by reducing hepatic fat deposition and metabolic derangement through modification of pathways underpinning liver fat oxidation, intestinal cholesterol efflux, energy metabolism and gut permeability. The hepatic and metabolic benefits induced by coffee were accompanied by changes in the gut microbiota.


Assuntos
Café/metabolismo , Dieta Hiperlipídica/efeitos adversos , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Acil-CoA Oxidase/metabolismo , Alanina Transaminase/sangue , Alcaligenaceae , Animais , Glicemia , Colesterol/sangue , Claudinas/metabolismo , Suplementos Nutricionais , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Haptoglobinas/metabolismo , Fígado/patologia , Masculino , Síndrome Metabólica , Camundongos , Camundongos Endogâmicos C57BL , PPAR alfa/metabolismo , Polifenóis/farmacologia , Precursores de Proteínas/metabolismo , RNA Mensageiro/metabolismo
7.
J Altern Complement Med ; 24(9-10): 933-941, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30247968

RESUMO

BACKGROUND: To address the side effects of anticancer treatments, the Clinic for Complementary Medicine and Diet in Oncology was opened, in collaboration with the oncology department, at the Hospital of Lucca (Italy) in 2013. AIM: To present the results of complementary medicine treatment targeted toward reducing the adverse effects of anticancer therapy and cancer symptoms, and improving patient quality of life. Dietary advice was aimed at the reduction of foods that promote inflammation in favor of those with antioxidant and anti-inflammatory properties. METHODS: This is a retrospective observational study on 357 patients consecutively visited from September 2013 to December 2017. The intensity of symptoms was evaluated according to a grading system from G0 (absent) to G1 (slight), G2 (moderate), and G3 (strong). The severity of radiodermatitis was evaluated with the Radiation Therapy Oncology Group (RTOG) scale. Almost all the patients (91.6%) were receiving or had just finished some form of conventional anticancer therapy. RESULTS: The main types of cancer were breast (57.1%), colon (7.3%), lung (5.0%), ovary (3.9%), stomach (2.5%), prostate (2.2%), and uterus (2.5%). Comparison of clinical conditions before and after treatment showed a significant amelioration of nausea, insomnia, depression, anxiety, fatigue, mucositis, hot flashes, joint pain, dysgeusia, neuropathy, and all symptoms. Moreover, in a subgroup of 17 patients in radiotherapy undergoing integrative treatment, the level of toxicities and the severity of radiodermatitis were much lower than in the 13 patients without integrative treatment. Twenty-one cancer patients (6.2%) either refused (18) or discontinued (3) conventional anticancer treatment against the recommendation of their oncologist; after the integrative oncology (IO) visit, 7 (41.2%) out of 17 patients with follow-up decided to accept standard oncologic treatments. CONCLUSIONS: An IO clinic may contribute to reducing the adverse effects of anticancer therapy and improving the quality of life of cancer patients.


Assuntos
Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Medicina Integrativa , Oncologia Integrativa , Neoplasias/terapia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Terapias Complementares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
United European Gastroenterol J ; 6(7): 1056-1064, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30228894

RESUMO

Background: The western diet high in fat and fructose may cause metabolic disorders and cardiovascular diseases. Objective: To evaluate whether long-term daily vitamin D3 supplementation prevents hepatic steatosis and cardiovascular abnormalities and restores insulin sensitivity caused by fat diet in rats without vitamin D deficiency. Methods: Three groups of rats were fed for 6 months with standard diet (SD), western diet (WD) or WD containing 23 IU/day/rat vitamin D3, respectively. Tail-cuff systolic blood pressure (SBP)measurements in conscious rats and transthoracic echocardiography were performed in basal condition, and after 3 and 6 months of diet. Hepatic steatosis and myocardial fibrosis were assessed in liver and cardiac tissues using standard methods. Serum insulin and 25(OH)D3 concentrations were determined using rat-specific ELISA kits. Insulin resistance was determined according to the homeostasis model assessment of insulin resistance (HOMA-IR) method. Results: Sixty-one per cent of hepatocytes in WD rats had steatotic vacuoles compared with just 27% in rats on a WD plus vitamin D3 (p < 0.05).HOMA-IR was reduced in rats with vitamin D supplementation compared with WD alone (19.4 ± 5.2 vs 41.9 ± 8.9, p < 0.05). Rat blood pressure and left ventricular mass were both reduced by vitamin D3 supplementation. Conclusion: In animal models of liver and cardiovascular metabolic damage, the supplementation of vitamin D3 shows liver and cardio-protective effects.

10.
Oncotarget ; 9(13): 10978-10986, 2018 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-29541390

RESUMO

For monitoring minimal residual disease (MRD) in chronic myeloid leukemia (CML) the most recommended method is quantitative RT-PCR (RT-qPCR) for measuring BCR-ABL1 transcripts. Several studies reported that a DNA-based assay enhances the sensitivity of detection of the BCR-ABL1 genomic rearrangement, even if its characterization results difficult. We developed a DNA-based method for detecting and quantifying residual BCR-ABL1 positive leukemic stem cells in CML patients. We propose two alternative approaches: the first one is a fluorescence in situ hybridization (FISH)-based step followed by Sanger sequencing; the second one employs MinION, a single molecule sequencer based on nanopore technology. Finally, after defining the BCR-ABL1 genomic junction, we performed the target CML patient-specific quantification, using droplet digital PCR (ddPCR). FISH and MinION steps, respectively, together with ddPCR analysis, greatly reduce the complexity that has impeded the use of "personalized monitoring" of CML in clinical practice. Our report suggests a feasible pipeline, in terms of costs and reproducibility, aimed at characterizing and quantifying the genomic BCR-ABL1 rearrangement during MRD monitoring in CML patients.

11.
Clin Lymphoma Myeloma Leuk ; 17(11): 767-773, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28864170

RESUMO

BACKGROUND: Patients with primary refractory or first relapse acute myeloid leukemia (AML) are considered to have worse clinical outcomes after treatment. For these patients, the achievement of complete remission appears crucial for them to be able to undergo allotransplantation, which might be the only possible treatment. PATIENTS AND METHODS: We used the FLAG-Ida (fludarabine, cytarabine [cytosine arabinoside], granulocyte colony-stimulating factor, idarubicin) regimen in patients with primary refractory/first relapse AML as a bridge to transplantation. We studied its efficacy in terms of overall response and overall survival to assess which variables (age, lactate dehydrogenase, bone marrow blast count, peripheral blood blast count, platelet count, white blood cell count, de novo or secondary AML, molecular-cytogenetic risk, duration of response, and relapsed or refractory disease) might have an effect on outcome. RESULTS: We analyzed the data from 108 consecutive adult patients (52 males, 66 females; median age, 49 years; range, 17-72 years) with newly diagnosed AML refractory to standard induction regimens or relapse after first complete remission, who had received the FLAG-Ida protocol as salvage therapy from January 2005 to December 2015. An overall response was achieved in 48 patients (44%). On multivariate analysis, the variables with a positive effect on the response rate were molecular-cytogenetic risk (P = .009), duration of first response in relapsed AML (P = .003), AML status (relapsed or refractory; P = .047), and peripheral blood blast count (P = .016). On multivariate analysis, overall survival was significantly associated with FLAG-Ida response (hazard ratio, 0.343; P = .001) and receipt of allotransplantation (hazard ratio, 0.277; P < .001). CONCLUSION: Our data seem to confirm the value of FLAG-Ida in this setting and might suggest its best usage as bridge therapy for patients awaiting allotransplantation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Alotransplante de Tecidos Compostos Vascularizados/métodos , Vidarabina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Citarabina/farmacologia , Citarabina/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Idarubicina/farmacologia , Idarubicina/uso terapêutico , Leucemia Mieloide Aguda/mortalidade , Masculino , Recidiva , Análise de Sobrevida , Vidarabina/farmacologia , Vidarabina/uso terapêutico
12.
Exp Mol Pathol ; 103(1): 33-37, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28663031

RESUMO

We report a third-generation sequencing assay on nanopore technology (MinION) for detecting BCR-ABL1 KD mutations and compare the results to a Sanger sequencing(SS)-based test in 24 Philadelphia-positive (Ph+) leukemia cases. Our data indicates that MinION is markedly superior to SS in terms of sensitivity, costs and timesaving, and has the added advantage of determining the clonal configuration of multiple mutations. We demonstrate that MinION is suitable for employment in the hematology laboratory for detecting BCR-ABL1 KD mutation in Ph+ leukemias.


Assuntos
Análise Mutacional de DNA , Proteínas de Fusão bcr-abl/genética , Sequenciamento de Nucleotídeos em Larga Escala , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Proteínas de Fusão bcr-abl/sangue , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Mutação , Nanoporos , Sensibilidade e Especificidade
13.
ACS Appl Mater Interfaces ; 9(31): 26531-26538, 2017 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-28742322

RESUMO

The mechanochemical reaction between copper and dimethyl disulfide is studied under well-controlled conditions in ultrahigh vacuum (UHV). Reaction is initiated by fast S-S bond scission to form adsorbed methyl thiolate species, and the reaction kinetics are reproduced by two subsequent elementary mechanochemical reaction steps, namely a mechanochemical decomposition of methyl thiolate to deposit sulfur on the surface and evolve small, gas-phase hydrocarbons, and sliding-induced oxidation of the copper by sulfur that regenerates vacant reaction sites. The steady-state reaction kinetics are monitored in situ from the variation in the friction force as the reaction proceeds and modeled using the elementary-step reaction rate constants found for monolayer adsorbates. The analysis yields excellent agreement between the experiment and the kinetic model, as well as correctly predicting the total amount of subsurface sulfur in the film measured using Auger spectroscopy and the sulfur depth distribution measured by angle-resolved X-ray photoelectron spectroscopy.

14.
Langmuir ; 33(23): 5657-5665, 2017 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28502183

RESUMO

Micropatterns and nanopatterns of gold embedded in silver and titanium embedded in gold have been prepared by combining either photolithography or electron-beam lithography with a glue-free template-stripping procedure. The obtained patterned surfaces have been topographically characterized using atomic force microscopy and scanning electron microscopy, showing a very low root-mean-square roughness (<0.5 nm), high coplanarity between the two metals (maximum height difference ≈ 2 nm), and topographical continuity at the bimetallic interface. Spectroscopic characterization using X-ray photoelectron spectroscopy (XPS), time-of-flight secondary-ion mass spectrometry (ToF-SIMS), and Auger electron spectroscopy (AES) has shown a sharp chemical contrast between the two metals at the interface for titanium patterns embedded in gold, whereas diffusion of silver into gold was observed for gold patterns embedded in silver. Surface flatness combined with a high chemical contrast makes the obtained surfaces suitable for applications involving functionalization with molecules by orthogonal adsorption chemistries or for instrumental calibration. The latter possibility has been tested by determining the image sharpness and the analyzed area on circular patterns of different sizes for each of the spectroscopic techniques applied for characterization.This is the first study in which the analyzed area has been determined using XPS and AES on a flat surface, and the first example of a method for determining the analyzed area using ToF-SIMS.

15.
Nat Nanotechnol ; 12(7): 642-647, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28436960

RESUMO

Iron-deficiency anaemia (IDA) is a major global public health problem. A sustainable and cost-effective strategy to reduce IDA is iron fortification of foods, but the most bioavailable fortificants cause adverse organoleptic changes in foods. Iron nanoparticles are a promising solution in food matrices, although their tendency to oxidize and rapidly aggregate in solution severely limits their use in fortification. Amyloid fibrils are protein aggregates initially known for their association with neurodegenerative disorders, but recently described in the context of biological functions in living organisms and emerging as unique biomaterial building blocks. Here, we show an original application for these protein fibrils as efficient carriers for iron fortification. We use biodegradable amyloid fibrils from ß-lactoglobulin, an inexpensive milk protein with natural reducing effects, as anti-oxidizing nanocarriers and colloidal stabilizers for iron nanoparticles. The resulting hybrid material forms a stable protein-iron colloidal dispersion that undergoes rapid dissolution and releases iron ions during acidic and enzymatic in vitro digestion. Importantly, this hybrid shows high in vivo iron bioavailability, equivalent to ferrous sulfate in haemoglobin-repletion and stable-isotope studies in rats, but with reduced organoleptic changes in foods. Feeding the rats with these hybrid materials did not result in abnormal iron accumulation in any organs, or changes in whole blood glutathione concentrations, inferring their primary safety. Therefore, these iron-amyloid fibril hybrids emerge as novel, highly effective delivery systems for iron in both solid and liquid matrices.


Assuntos
Amiloide , Sistemas de Liberação de Medicamentos , Ferro , Lactoglobulinas , Nanopartículas Metálicas , Amiloide/química , Amiloide/farmacocinética , Amiloide/farmacologia , Anemia Ferropriva/tratamento farmacológico , Animais , Coloides , Alimentos Fortificados , Humanos , Ferro/química , Ferro/farmacocinética , Ferro/farmacologia , Lactoglobulinas/química , Lactoglobulinas/farmacocinética , Lactoglobulinas/farmacologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Ratos
16.
ACS Omega ; 2(11): 7790-7802, 2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31457337

RESUMO

NiP alloys are very often used in industry, due to their outstanding performance in corrosion and wear. Alloys with high phosphorus content (≥16 atom % P) are amorphous and show high corrosion resistance in both neutral and acidic solutions irrespective of the presence of chloride ions. The reason for this behavior is attributed to the formation of a "P-enriched surface layer" whose exact nature is still under debate. In this work, an iterative algorithm based on the application of maximum entropy method on nondestructive angle-resolved X-ray photoelectron spectroscopy data has been applied to the investigation of the surface layer grown on Ni18P alloys following mechanical polishing and anodic polarization in sulfate solutions. The results show that the outermost region of the examined alloy has a complex layered structure: (1) an uppermost hydrocarbon contamination layer about 1 nm thick, which includes also adsorbed water; (2) a nickel (poly)phosphate layer of about 1 nm; (3) a highly phosphorus-enriched interface being about 2 nm thick with a marked phosphorus concentration gradient, from 70 to 20 atom %; and (4) bulk alloy with the stoichiometric composition. These findings, together with the chemical state of the different phosphorus compounds, allow us to conclude that the high corrosion and wear resistance of NiP alloys might be ascribed to the presence of a thin, self-repairing nickel (poly)phosphate layer grown on a strongly P-enriched interface. Because the Auger parameter of P at the interface is similar to that of elemental P, it might be also concluded that the interface is enriched in elemental phosphorus.

17.
Neoplasia ; 18(9): 536-40, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27659013

RESUMO

Dasatinib (DAS) has been licensed for the frontline treatment in chronic myeloid leukemia (CML). However, very few data are available regarding its efficacy and toxicity in elderly patients with CML outside clinical trials. To address this issue, we set out a "real-life" cohort of 65 chronic phase CML patients older than 65 years (median age 75.1 years) treated frontline with DAS in 26 Italian centers from June 2012 to June 2015, focusing our attention on toxicity and efficacy data. One third of patients (20/65: 30.7%) had 3 or more comorbidities and required concomitant therapies; according to Sokal classification, 3 patients (4.6%) were low risk, 39 (60.0%) intermediate risk, and 20 (30.8%) high risk, whereas 3 (4.6%) were not classifiable. DAS starting dose was 100 mg once a day in 54 patients (83.0%), whereas 11 patients (17.0%) received less than 100 mg/day. Grade 3/4 hematologic and extrahematologic toxicities were reported in 8 (12.3%) and 12 (18.5%) patients, respectively. Overall, 10 patients (15.4%) permanently discontinued DAS because of toxicities. Pleural effusions (all WHO grades) occurred in 12 patients (18.5%) and in 5 of them occurred during the first 3 months. DAS treatment induced in 60/65 patients (92.3%) a complete cytogenetic response and in 50/65 (76.9%) also a major molecular response. These findings show that DAS might play an important role in the frontline treatment of CML patients >65 years old, proving efficacy and having a favorable safety profile also in elderly subjects with comorbidities.


Assuntos
Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Bandeamento Cromossômico , Estudos de Coortes , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Seguimentos , Proteínas de Fusão bcr-abl/genética , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Gradação de Tumores , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Resultado do Tratamento
18.
Oncotarget ; 7(48): 80083-80090, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27579540

RESUMO

BACKGROUND: About 40% of all patients with chronic myeloid leukemia are currently old or very old. They are effectively treated with imatinib, even though underrepresented in clinical studies. Furthermore, as it happens in the general population, they often receive multiple drugs for associated chronic illnesses. Aim of this study was to assess whether or not in imatinib-treated patients aged >75 years the exposure to polypharmacy (5 drugs or more) had an impact on cytogenetic and molecular response rates, event-free and overall survival, as well as on hematological or extra-hematological toxicity. METHODS: 296 patients at 35 Italian hematological institutions were evaluated. RESULTS: Polypharmacy was reported in 107 patients (36.1%), and drugs more frequently used were antiplatelets, diuretics, proton pump inhibitors, ACE-inhibitors, beta-blockers, calcium channel blockers, angiotensin II receptors blockers, statins, oral hypoglycemic drugs and alpha blockers. Complete cytogenetic response was obtained in 174 patients (58.8%), 78 (26.4%) within 6 month, 63 (21.3%) between 7 and 12 months. Major molecular response was obtained in 153 patients (51.7%), 64 (21.6%) within the 12 month. One hundred and twenty-eight cases (43.2%) of hematological toxicity were recorded, together with 167 cases (56.4%) of extra-hematological toxicity. Comparing patients exposed to polypharmacy to those without, no difference was observed pertaining to the dosage of imatinib, cytogenetic and molecular responses and hematological and extra-hematological toxicity. CONCLUSION: Notwithstanding the several interactions reported in the literature between imatinib and some of the medications considered herewith, this fact does not seem to have a clinical impact on response rate and outcome.


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Polimedicação , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Masculino , Resultado do Tratamento
19.
Phys Chem Chem Phys ; 18(32): 22719-30, 2016 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-27430333

RESUMO

With reference to our previous surface-force study on 1-hexyl-3-methylimidazolium ethylsulfate ([HMIM] EtSO4) using an extended surface forces apparatus, which showed an ordered structure within the nanoconfined dry ionic liquid (IL) between mica surfaces that extended up to ∼60 nm from the surface, this work focuses on the influence of the environmental humidity on the bulk, interfacial and nanoconfined structure of [HMIM] EtSO4. Infrared spectroscopy and rheometry reflect the changes in chemical and physical properties of the bulk IL due to the uptake of water when exposed to ambient humidity, while wide-angle X-ray scattering shows a mild swelling of the bulk nanostructure, and the AFM sharp tip reveals an additional surface layer at the mica-IL interface. When the water-containing [HMIM] EtSO4 is nanoconfined between two mica surfaces, no long-range order is detected, in contrast to the results obtained for the dry IL, which demonstrates that the presence of water can prevent the liquid-to-solid transformation of this IL. A combination of techniques and the calculated Bjerrum length indicate that water molecules weaken interionic electrostatic and hydrogen-bonding interactions, which lessens ion-ion correlations. Our work shows that the solid-like behavior of the nanoconfined IL strongly depends on the presence of absorbed water and hence, it has implications with regard to the correct interpretation of laboratory studies and their extension to real applications in lubrication.

20.
Nanoscale ; 8(7): 4094-106, 2016 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-26821595

RESUMO

Understanding the behavior of ionic liquids (ILs) either confined between rough surfaces or in rough nanoscale pores is of great relevance to extend studies performed on ideally flat surfaces to real applications. In this work we have performed an extensive investigation of the structural forces between two surfaces with well-defined roughness (<9 nm RMS) in 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide by atomic force microscopy. Statistical studies of the measured layer thicknesses, layering force, and layering frequency reveal the ordered structure of the rough IL-solid interface. Our work shows that the equilibrium structure of the interfacial IL strongly depends on the topography of the contact.

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