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1.
Anal Chem ; 96(26): 10577-10585, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38887964

RESUMO

Simultaneous detection of multiple breast cancer-associated miRNAs significantly raises the accuracy and reliability of early diagnosis. In this work, disposable carbon fiber paper serves as the biosensing interface, linking DNA probes via click chemistry to efficiently capture targets and signals efficiently. DNA probes have multiple recognition domains that trigger a cascade reaction through the helper probes and targets, resulting in two signals output. The signals are centrally encapsulated in the pore of the MIL-88(Fe)-NH2. The signal carriers are directed by signal probes to the recognition domains that correspond to the DNA probes. The biosensor is selective and stable, and it can quantify miRNA-21 and miRNA-155 simultaneously with detection limits of 0.64 and 0.54 fmol/L, respectively. Furthermore, it demonstrates satisfactory performance in tests conducted with normal human serum and cell lysate. Overall, this method makes a satisfactory exploration to realize an inexpensive and sensitive biosensor for multiple biomarkers.


Assuntos
Técnicas Biossensoriais , Química Click , MicroRNAs , Técnicas Biossensoriais/métodos , Humanos , MicroRNAs/análise , MicroRNAs/sangue , Sondas de DNA/química , Neoplasias da Mama/diagnóstico , Limite de Detecção
2.
Anal Chem ; 96(18): 6930-6939, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38652001

RESUMO

Circulating tumor DNA (ctDNA) holds great promise as a noninvasive biomarker for cancer diagnosis, treatment, and prognosis. However, the accurate and specific quantification of low-abundance ctDNA in serum remains a significant challenge. This study introduced, for the first time, a novel exponential amplification reaction (EXPAR)-assisted CRISPR/Cas12a-mediated ratiometric dual-signal electrochemical biosensor for ultrasensitive and reliable detection of ctDNA. To implement the dual-signal strategy, a signal unit (ssDNA-MB@Fc/UiO-66-NH2) was prepared, consisting of methylene blue-modified ssDNA as the biogate to encapsulate ferrocene signal molecules within UiO-66-NH2 nanocarriers. The presence of target ctDNA KRAS triggered EXPAR amplification, generating numerous activators for Cas12a activation, resulting in the cleavage of ssDNA-P fully complementary to the ssDNA-MB biogate. Due to the inability to form a rigid structure dsDNA (ssDNA-MB/ssDNA-P), the separation of ssDNA-MB biogate from the UiO-66-NH2 surface was hindered by electrostatic interactions. Consequently, the supernatant collected after centrifugation exhibited either no or only a weak presence of Fc and MB signal molecules. Conversely, in the absence of the target ctDNA, the ssDNA-MB biogate was open, leading to the leakage of Fc signal molecules. This clever ratiometric strategy with Cas12a as the "connector", reflecting the concentration of ctDNA KRAS based on the ratio of the current intensities of the two electroactive signal molecules, enhanced detection sensitivity by at least 60-300 times compared to single-signal strategies. Moreover, this strategy demonstrated satisfactory performance in ctDNA detection in complex human serum, highlighting its potential for cancer diagnosis.


Assuntos
Técnicas Biossensoriais , DNA Tumoral Circulante , Técnicas Eletroquímicas , Humanos , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Sistemas CRISPR-Cas/genética , DNA de Cadeia Simples/química , Limite de Detecção , Endodesoxirribonucleases/química , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Associadas a CRISPR/química , Proteínas de Bactérias/química , Proteínas de Bactérias/genética
3.
Anal Chem ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028987

RESUMO

Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki67 are four crucial biomarkers used in the clinical diagnosis of breast cancer. Accurate detection of these biomarkers is essential for an effective diagnosis and treatment. MOF-based micronano motors (MOFtors) are promising for various applications, including environmental remediation, targeted nanosurgery, and biomarker detection. This paper presents a clinically feasible diagnostic electrochemical micronano motor biosensor, built on a miniature swimmer, for the multiplex detection and grading of breast cancer biomarkers. We designed a biosensor, named MOFtor-MSEM, incorporating aptamers and antibodies functionalized on SiO2@Co-Fe-MOF, which acts as a miniature swimmer in solution. The SiO2@Co-Fe-MOF serves as the body, while complementary double-chain-linked antibodies function as paddles. In a homogeneous solution, when a positive voltage is applied to the working electrode, the electrostatic interaction between the neutral SiO2@Co-Fe-MOF and the negatively charged complementary double-linked antibody causes the antibody to move toward the electrode and then regress due to water resistance. This back-and-forth motion propels the miniature swimmer, enabling it to move the target analyte through the solution. The sensor features an automatic "sample-amplifying signal-output" process, achieving simultaneous signal amplification and output of four electrochemical signals on a single nanomaterial, a significant challenge in electrochemical sensing. The biosensor boasts a short detection time of 40 min, compared to approximately 1 week for current clinical tissue testing. Additionally, the bioplatform selectively detects HER2, ER, Ki67, and PR in the range of 0-1500 pg/mL, with detection limits of 0.01420, 0.03201, 0.01430, and 0.01229 pg/mL, respectively.

4.
Anal Chem ; 96(12): 4774-4782, 2024 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-38477105

RESUMO

Circulating tumor DNA (ctDNA), as a next-generation tumor marker, enables early screening and monitoring of cancer through noninvasive testing. Exploring the development of new methods for ctDNA detection is an intriguing study. In this work, a unique electrochemical biosensor for the ctDNA detector was constructed in the first utilizing Fe single-atom nanozymes-carbon dots (SA Fe-CDs) as a signaling carrier in collaboration with a DNA walker cascade amplification strategy triggered by nucleic acid exonuclease III (Exo III). The electrochemical active surface area of AuNPs/rGO modified onto a glassy carbon electrode (AuNPs/rGO/GCE) was about 1.43 times that of a bare electrode (bare GCE), with good electrical conductivity alongside a high heterogeneous electron transfer rate (5.81 × 10-3 cm s-1), that is, as well as the ability to load more molecules. Sequentially, the DNA walker cascade amplification strategy driven by Exo III effectively converted the target ctDNA into an amplified biosignal, ensuring the sensitivity and specificity of ctDNA. Ultimately, the electrochemical signal was further amplified by introducing SA Fe-CDs nanozymes, which could serve as catalysts for 3,3',5,5'-tetramethylbenzidine (TMB) oxidation with facile responding (Vmax = 0.854 × 10-6 M s-1) and robust annexation (Km = 0.0069 mM). The integration of the triple signal amplification approach achieved detection limits as low as 1.26 aM (S/N = 3) for a linearity spanning from 5 aM to 50 nM. In this regard, our proposal for a biosensor with exceptional assay properties in complicated serum environments had great potential for early and timely diagnosis of cancer.


Assuntos
Técnicas Biossensoriais , DNA Tumoral Circulante , Exodesoxirribonucleases , Nanopartículas Metálicas , Neoplasias , Ácidos Nucleicos , Humanos , Carbono , Ouro/química , Técnicas Eletroquímicas/métodos , Limite de Detecção , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos
6.
Am J Hematol ; 99(3): 380-386, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38258329

RESUMO

Acute myeloid leukemia (AML) in older patients has a poor prognosis, low complete remission (CR) rates, and poor overall survival (OS). Preclinical studies have shown synergistic effects of epigenetic priming with hypomethylating agents followed by cytarabine. Based on these data, we hypothesized that an induction regimen using epigenetic priming with decitabine, followed by cytarabine would be effective and safe in older patients with previously untreated AML. Here, we conducted a phase 2 trial in which older patients with previously untreated AML received an induction regimen consisting of 1 or 2 courses of decitabine 20 mg/m2 intravenously (IV) for 5 days followed by cytarabine 100 mg/m2 continuous IV infusion for 5 days. Forty-four patients (median age 76 years) were enrolled, and CR/CRi was achieved by 26 patients (59% of all patients, 66.7% of evaluable patients). Fourteen of 21 (66.7%) patients with adverse cytogenetics achieved CR including six out of seven evaluable patients with TP53 mutations. The 4- and 8-week mortality rates were 2.3% and 9.1%, respectively, with median OS of 10.7 months. These results suggest epigenetic priming with decitabine followed by cytarabine should be considered as an option for first-line therapy in older patients with AML. This trial was registered at www.clinicaltrials.gov as # NCT01829503.


Assuntos
Citarabina , Leucemia Mieloide Aguda , Idoso , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Decitabina , Epigênese Genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Indução de Remissão , Resultado do Tratamento
7.
Anal Chem ; 95(32): 12122-12130, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37527175

RESUMO

Accurate detection of cancer-associated mRNAs is beneficial to early diagnosis and potential treatment of cancer. Herein, for the first time, we developed a novel CRISPR/Cas12a-powered electrochemical/fluorescent (EC/FL) dual-mode controlled-release homogeneous biosensor for mRNA detection. A functionalized ssDNA P2-capped Fe3O4-NH2 loaded with methylene blue (P2@MB-Fe3O4-NH2) was synthesized as the signal probe, while survivin mRNA was chosen as the target RNA. In the presence of the target mRNA, the nicking endonuclease-mediated rolling circle amplification (NEM-RCA) was triggered to produce significant amounts of ssDNA, activating the collateral activity of Cas12a toward the surrounding single-stranded DNA. Thus, the ssDNA P1 completely complementary to ssDNA P2 was cleaved, resulting in that the ssDNA P2 bio-gate on Fe3O4-NH2 could not be opened due to electrostatic interactions. As a result, there was no or only a little MB in the supernatant after magnetic separation, and the measured EC/FL signal was exceedingly weak. On the contrary, the ssDNA P2 bio-gate was opened, enabling MB to be released into the supernatant, and generating an obvious EC/FL signal. Benefiting from the accuracy of EC/FL dual-mode cross-verification, high amplification efficiency, high specificity of NEM-RCA and CRISPR/Cas12a, and high loading of mesoporous Fe3O4-NH2 on signal molecules, the strategy shows aM-level sensitivity and single-base mismatch specificity. More importantly, the practical applicability of this dual-mode strategy was confirmed by mRNA quantification in complex serum environments and tumor cell lysates, providing a new way for developing a powerful disease diagnosis tool.


Assuntos
Técnicas Biossensoriais , Sistemas CRISPR-Cas , Sistemas CRISPR-Cas/genética , Preparações de Ação Retardada , RNA Mensageiro/genética , RNA , Corantes , DNA de Cadeia Simples/genética , Endonucleases , Inibidores de Serina Proteinase
8.
Hematol Oncol ; 41(4): 743-752, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37086447

RESUMO

Relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) is a genetically complex and heterogeneous disease with a poor prognosis and limited treatment options. Thus, there is an urgent need to develop therapeutic combinations to overcome drug resistance in AML. This open-label, multicenter, international, phase 1b study evaluated the safety, efficacy, and pharmacokinetics of venetoclax in combination with alvocidib in patients with R/R AML. Patients were treated with escalating doses of venetoclax (400, 600, and 800 mg QD, orally, days 1-28) and alvocidib (45 and 60 mg/m2 , intravenously, days 1-3) in 28-day cycles. The combination was found to be safe and tolerable, with no maximum tolerated dose reached. Drug-related Grade ≥3 adverse events were reported in 23 (65.7%) for venetoclax and 24 (68.6%) for alvocidib. No drug-related AEs were fatal. Gastrointestinal toxicities, including diarrhea, nausea, and vomiting were notable and frequent; otherwise, the toxicities reported were consistent with the safety profile of both agents. The response rate was modest (complete remission [CR] + incomplete CR [CRi], 11.4%; CR + CRi + partial response rate + morphologic leukemia-free state, 20%). There was no change in alvocidib pharmacokinetics with increasing doses of venetoclax. However, when venetoclax was administered with alvocidib, AUC24 and Cmax decreased by 18% and 19%, respectively. A recommended phase 2 dose was not established due to lack of meaningful increase in efficacy across all cohorts compared to what was previously observed with each agent alone. Future studies could consider the role of the sequence, dosing, and the use of a more selective MCL1 inhibitor for the R/R AML population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia Mieloide Aguda , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/etiologia
9.
Anal Bioanal Chem ; 415(27): 6647-6661, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37848579

RESUMO

Detection of human-generated volatile organic compounds (VOCs) is a new pathway for assessing health. Herein, a polyvinylidene fluoride (PVDF)-based colorimetric sensor array was designed for detecting disease-related VOCs (DVOCs) within 15 min, using a complex of Cu metal-organic framework, graphene aerogel, and dyes as response materials. Fingermaps derived from 28 DVOCs were obtained for further data processing. Pattern recognition was successfully employed in the correct discrimination of 28 DVOCs in low (10 µM), medium (100 µM), and high (300 µM) concentrations. Importantly, the sensor array also presented excellent discrimination ability and application potential when detecting VOCs produced by human cancer and normal cells. In general, VOC acquisition is noninvasive and harmless, and the PVDF-based sensor arrays are simple and visual. Such advantages expand their further application potential.


Assuntos
Neoplasias , Compostos Orgânicos Voláteis , Humanos , Colorimetria , Polivinil , Neoplasias/diagnóstico
10.
Appl Opt ; 62(6): A127-A136, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36821331

RESUMO

Trace detection of toxic heavy metals is a very important and difficult problem in several areas: convenience, sensitivity, and reliability. Herein, we develop an innovative fluorescence resonance energy transfer (FRET)-based ratio fluorescence sensor for the detection of heavy metal mercury ion (H g 2+). The sensing platform is composed of coumarin derivatives (CDs) and a copper metal-organic framework (Cu-MOF) named CD/Cu-MOF. The constructed CD/Cu-MOFs ratio fluorescence sensor exhibits dual emission peaks at 430 and 505 nm under the single excitation wavelength of 330 nm. With the addition of H g 2+, the fluorescence intensity of the system at 430 nm gradually increased, and the fluorescence intensity at 505 nm remained stable, resulting in a change in the fluorescence ratio. There is a good logarithmic relationship between the H g 2+ concentration in the range from 2×10-8 to 0.001 nM and the ratio of the fluorescence emission intensity of the system (F 430/F 505) (R 2=0.9901), and its calculated detection limit is 3.76×10-9 n M. In addition, the CD/Cu-MOFs ratio fluorescence sensor has achieved a good recovery rate of standard addition in the actual food sample recovery experiment, which provides an effective method for the detection of H g 2+ in food samples.

11.
Anal Chem ; 94(50): 17653-17661, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36473113

RESUMO

The untested empirical medications exacerbated the development of multidrug-resistant Mycobacterium tuberculosis (MDR-TB). Here, we develop a rapid and specific method based on loop-mediated isothermal amplification and duplex-specific nuclease for distinguishing rifampicin-resistant M. tuberculosis. Three probes were designed for the codons 516, 526, and 531 on the RNA polymerase ß-subunit (rpoB) gene. These three sites accounted for more than 90% of the total mutations of the ropB gene in the rifampicin-resistant strain. The approach can perform simultaneous and sensitive detection of three mutant sites with the actual detection limit as 10 aM of DNA and 62.5 cfu·mL-1 of bacteria in 67 min under isothermal conditions. Moreover, the positive mode of the approach for MDR-TB can not only deal with the randomness and diversity of mutations but also provide an easier way for medical staff to read the results. Therefore, it is a particularly valuable method to handle major and urgent MDR-TB diagnostics.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Rifampina , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Mutação , RNA Polimerases Dirigidas por DNA/genética , Antituberculosos , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/genética
12.
Blood ; 135(24): 2137-2145, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32219442

RESUMO

Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Sulfonamidas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Indução de Remissão , Resultado do Tratamento
13.
Support Care Cancer ; 30(2): 1673-1679, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34562168

RESUMO

PURPOSE: Central venous catheters (CVCs) are widely used in acute myeloid leukemia (AML) patients. Complications associated with CVCs are frequently encountered and contribute to morbidity and mortality. Prospective studies investigating and comparing complications of different types of CVCs in AML patients and their effects on the quality of life are limited. METHODS: We conducted a prospective observational study and evaluated the complications associated with the use of CVCs in adult AML patients during induction chemotherapy and evaluated quality of life outcomes as reported by the patients during and after their hospitalization. RESULTS: Fifty newly diagnosed patients with AML (median age, 59 years) who received intensive induction chemotherapy were enrolled in the study. Twenty-nine patients (58%) had a peripherally inserted central catheters (PICCs) placed and 21 (42%) patients received a Hickmann tunneled central catheter (TCC). Three percent of cases developed catheter-related thrombosis in PICCs and no thrombosis in TCCs. Catheter-related bloodstream infection was diagnosed in 8% of patients. CVC occlusion occurred in 44 patients (88%). The total number of occlusion events was 128; 97% of patients with PICCs and 76% of patients with TCCs (p = 0.003). All patients reported that the use of CVC simplified their course of treatment. Most patients reported similar restrictions in activity associated with TCCs and PICCs. CONCLUSION: The present study demonstrates that thrombosis and catheter-related bloodstream infections remain important complications of CVCs in AML patients. Occlusion rates were higher with the use of PICCs and the use of CVCs impacted the quality of life.


Assuntos
Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Cateterismo Periférico , Cateteres Venosos Centrais , Leucemia Mieloide Aguda , Adulto , Infecções Relacionadas a Cateter/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco
14.
Future Oncol ; 17(35): 4959-4969, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34783255

RESUMO

Aim: A retrospective chart review of ibrutinib-treated patients with chronic lymphocytic leukemia (CLL) was conducted. Patients & methods: Adults with CLL who initiated ibrutinib were followed for ≥6 months (n = 180). Results: Twenty-five percent of first-line ibrutinib patients experienced ≥1 dose reduction, mainly due to adverse events (AEs; 79%). Treatment discontinuations and dose holds occurred in 20 and 34% of patients, respectively, most commonly due to AEs (73 and 74%). Approximately one-quarter of relapsed/refractory ibrutinib patients experienced ≥1 dose reduction, mainly due to AEs (88%). Treatment discontinuation and dose holds occurred in 40% of patients (58 and 76% due to AEs, respectively). Conclusion: Dose reductions, holds and discontinuations were frequent in patients with CLL receiving ibrutinib in routine clinical practice.


Lay abstract Chronic lymphocytic leukemia (CLL) is a cancer that develops from a type of white blood cells called 'B cells.' Ibrutinib is a targeted therapy that inhibits the activity of a protein called Bruton's tyrosine kinase, which plays a key role in CLL. Patients receiving ibrutinib treatment can experience side effects ('adverse events'). In addition, patients may need to reduce their drug dose ('dose reductions') or stop treatment ('discontinuations') for a variety of reasons. We reviewed patients' charts to describe dose reductions and discontinuations in ibrutinib-treated patients with CLL. Our results indicate that dose reductions and discontinuations were frequent in patients with CLL receiving ibrutinib in routine clinical practice, and that the most common reason was adverse events.


Assuntos
Adenina/análogos & derivados , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Piperidinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Adenina/administração & dosagem , Adenina/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Gerenciamento Clínico , Resistencia a Medicamentos Antineoplásicos , Redução da Medicação , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/etiologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Recidiva , Estudos Retrospectivos , Suspensão de Tratamento
15.
Sensors (Basel) ; 20(5)2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32182908

RESUMO

A facile and effective colorimetric-sensing platform based on the diazotization of phenosafranin for the detection of NO 2 - under acidic conditions using the Griess assay is presented. Diazotization of commercial phenosafranin produces a color change from purplish to blue, which enables colorimetric quantitative detection of NO 2 - . Optimal detection conditions were obtained at a phenosafranin concentration of 0.25 mM, HCl concentration of 0.4 M, and reaction time of 20 min. Under the optimized detection conditions, an excellent linearity range from 0 to 20 µM was obtained with a detection limit of 0.22 µM. Favorable reproducibility and selectivity of the colorimetric sensing platform toward NO 2 - were also verified. In addition, testing spiked ham sausage, bacon, and sprouts samples demonstrated its excellent practicability. The presented colorimetric sensing platform is a promising candidate for the detection of NO 2 - in real applications.

17.
Mikrochim Acta ; 186(4): 259, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30923924

RESUMO

A fluorometric method was developed for the determination of the insecticide cartap. It is based on the use of green emitting carbon dots (CDs) and gold nanoparticles (Au NPs). The CDs were prepared from phenol and ethylene diamine by a hydrothermal route. They have excitation/emission maxima at 410/513 nm) and a fluorescence quantum yield of 29%. They were characterized by TEM, Raman, XRD, XPS, FT-IR, UV and fluorescence spectroscopies. The green fluorescence of the CDs is strongly reduced by the red-colored Au NPs because of an inner filter effect. Upon addition of cartap, it will cause the aggregation of the Au NPs owing to Au-N interaction between Au NPs and cartap to form purple colored aggregates with spectra that do not overlap the green emission of the CDs. Hence, their fluorescence is restored. Under optimum conditions, the method allows for the quantitation of cartap in the 5-300 nM concentration range, and the detection limit is 3.8 nM. The method was successfully applied to the determination of cartap in spiked real samples and gave satisfactory results. Graphical abstract Schematic presentation of green emitting carbon dots for sensitive fluorometric determination of cartap based on its aggregation effect on gold nanoparticles.

18.
Sensors (Basel) ; 18(9)2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30200221

RESUMO

In this study, two new quasi-three-dimensional Surface Enhanced Raman Scattering (SERS) substrates, namely porous Ag and Ag-NiO nanofibrous mats, were prepared using a simple, electrospinning-calcination, two-step synthetic process. AgNO3/polyvinyl pyrrolidone (PVP) and AgNO3/Ni(NO3)2/PVP composites serving as precursors were electrospun to form corresponding precursory nanofibers. Porous Ag and Ag-NiO nanofibers were successfully obtained after a 3-h calcination at 500 °C under air atmosphere, and analyzed using various material characterization techniques. Synthesized, quasi-three-dimensional porous Ag and Ag-NiO nanofibrous mats were applied as SERS substrates, to measure the model compound Rhodamine 6G (R6G), and investigate the corresponding signal enhancement. Furthermore, porous Ag and Ag-NiO nanofibrous mats were employed as SERS substrates for melamine and methyl parathion respectively. Sensitive detection of melamine and methyl parathion was achieved, indicating their feasibility as an active SERS sensing platform, and potential for food safety and environmental monitoring. All the results suggest that the electrospinning-calcination, two-step method offers a new, low cost, high performance solution in the preparation of SERS substrates.

19.
Cytotherapy ; 19(10): 1225-1232, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28864289

RESUMO

BACKGROUND AIMS: Activated NK cells (aNK) generated by expansion of a human interleukin-2-dependent NK cell line (NK-92) were shown to mediate strong anti-leukemia activity. This phase 1 study evaluated feasibility, safety, and activity of aNK cells adoptively transferred to patients with refractory/relapsed acute myeloid leukemia (AML). In addition, effects of these aNK cells on the patient's immune system were evaluated. METHODS: Two cell-dose levels (1 × 109 cells/m2 and 3 × 109 cells/m2) were used. One treatment course consisted of two infusions of the same cell dose, each cell infusion delivered 24 h apart. The aNK cells were administered in the outpatient setting. RESULTS: Seven patients with refractory/relapsed AML were treated with a total of 20 aNK cell infusions. None of the 7 patients experienced dose-limiting toxicities during the aNK cell administration or during 21 days of the post-infusion observation period. No grade 3-4 toxicities (probable or definite) related to aNK cell infusions occurred. Activity was transient in 3 of 7 patients. No significant changes in the patient's lymphocyte counts, subsets frequency, phenotype or activity were observed post-infusion. Cell dose-dependent effects in the plasma levels of several cytokines were observed. DISCUSSION: The trial demonstrated the safety and feasibility of adoptive cell therapy with "off-the-shelf" aNK cells in patients with refractory/relapsed AML. These data provide the foundation for future combination immunotherapy trials and for the optimization of aNK cell based therapies in patients with AML.


Assuntos
Imunoterapia Adotiva/métodos , Células Matadoras Naturais/transplante , Leucemia Mieloide Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Transplante de Células/efeitos adversos , Transplante de Células/métodos , Citocinas/sangue , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Interleucina-2/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
20.
Clin Transplant ; 31(9)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28710776

RESUMO

Organ transplant recipients are at an increased risk for subsequent cancer including acute myeloid leukemia (AML). Treatment of AML following solid transplantation represents a clinical challenge as most patients have significant comorbidities at the time of AML diagnosis. In this study, we evaluated the treatment and outcomes of patients who developed AML following solid organ transplantation at our institution and reviewed the literature on outcomes for these patients. The study cohort consisted of 14 patients (median age 66 years, range 52-77 years) with newly diagnosed AML following solid organ transplantation. The median interval time between solid organ transplantation and AML diagnosis was 72 months (range 15-368 months). Seven patients received standard induction chemotherapy, four patients received intermediate type therapy, and the remaining three patients were deemed not fit for therapy and received palliative and supportive care. Six of the 11 treated patients (55%) achieved complete remission (CR). The median overall survival (OS) for all patients was 6 months. The median OS for the patients who achieved complete remission after therapy was 17 months and 2 months for the remaining patients. Despite initial CR, relapse rates are still high, suggesting that alternative strategies for post-remission therapies are warranted.


Assuntos
Leucemia Mieloide Aguda/etiologia , Transplante de Órgãos , Complicações Pós-Operatórias , Idoso , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Análise de Sobrevida , Resultado do Tratamento
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