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1.
Nature ; 598(7879): 35-37, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34616051
2.
Lung Cancer ; 161: 180-188, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34607210

RESUMO

OBJECTIVES: Both combinations of the PARP inhibitor veliparib plus platinum doublet chemotherapy (CT), and the programmed death receptor-1 (PD-1) inhibitor nivolumab plus CT have demonstrated encouraging efficacy for treatment of non-small cell lung cancer (NSCLC). This phase 1 dose-escalation study (NCT02944396) evaluated the quadruple combination of veliparib with nivolumab and doublet CT in patients with unresectable advanced/metastatic NSCLC. MATERIALS AND METHODS: Patients were enrolled into five dosing cohorts: patients received veliparib 120 mg twice daily (BID) combined with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and paclitaxel 200 mg/m2 (C/PAC) or veliparib 80/120/200/240 mg BID in combination with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and pemetrexed 500 mg/m2 (C/PEM). Primary objective was to identify the recommended phase 2 dose (RP2D) of veliparib + nivolumab + CT. Safety, tolerability, and efficacy of this combination were also assessed. RESULTS: Twenty-five patients were enrolled: 6 patients received veliparib 120 mg BID + nivolumab + C/PAC and 19 received veliparib (80-240 mg BID) + nivolumab + C/PEM. No dose-limiting toxicities were reported, and the RP2Ds were veliparib 120 mg BID + nivolumab + C/PAC, and veliparib 240 mg BID + nivolumab + C/PEM. The most common any-grade adverse events (AEs) were fatigue (56%), nausea (52%), and anemia (48%). Grade 3/4 AEs included anemia (32%) and neutropenia (24%), and the most frequent serious AE was malignant neoplasm progression (12%). Veliparib exhibited approximately dose proportional kinetics in the dose range 80-240 mg BID combined with nivolumab and C/PEM, with no effects on pemetrexed pharmacokinetics. Overall, the confirmed objective response rate was 40%, and best overall response was 64%. CONCLUSION: Veliparib combined with nivolumab and platinum doublet CT was tolerated in patients with advanced/metastatic NSCLC, and no evidence of drug-drug interaction was observed. Although preliminary, this quadruple therapy may have promising antitumor activity.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzimidazóis , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Platina/uso terapêutico
3.
Anticancer Res ; 41(10): 4687-4695, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593416

RESUMO

Remarkable developments in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been achieved over the past decade. Although targeting the novel androgen receptor axis and using chemotherapeutic agents have improved survival, mCRPC is still a lethal disease. A better molecular characterization of cancer resulted in the determination of the important role of homologous recombination repair (HRR) genes in cancer development, and poly (ADP-ribose) polymerase (PARP) is one of the most attractive therapeutic targets. Recent clinical studies have demonstrated that PARP inhibitors significantly improve oncological outcomes in patients with mCRPC harboring BRCA mutations, and PARP inhibitors are becoming a standard of care for these patients. However, not only PARP inhibitors, but also chemotherapeutic agents such as platinum agents, taxanes, and radium-223 are active in HRR gene mutation carriers, and platinum sensitivity may predict the efficacy of PARP inhibitors for mCRPC. The combination of PARP inhibitors with other anti-cancer agents may overcome resistance mechanisms against PARP inhibitors and lead to survival benefits. Appropriate treatment sequences and combinations may change the therapeutic landscape of DNA repair deficient mCRPC.


Assuntos
Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Mutação , Platina/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Reparo de DNA por Recombinação/genética , Resultado do Tratamento
4.
Anal Chim Acta ; 1182: 338935, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34602208

RESUMO

Toxicological studies of nanoparticles (NPs) are highly demanded nowadays but they are very challenging. In the in vitro assays, the understanding of the role of cell culture media is crucial to derive a proper interpretation of the toxicological results and to do so, new analytical tools are necessary. In this context, an analytical strategy based on reversed-phase liquid chromatography hyphenated to inductively coupled plasma-triple quadrupole mass spectrometry (HPLC-ICP-TQ-MS) has been developed for the first time for the detection and characterization of both 5 and 30 nm PtNPs, as well as ionic platinum species, in commonly used cell culture media. For this purpose, Dulbecco's Modified Eagle Medium, DMEM-high glucose, DMEM-F12, DMEM 31053-028, and Roswell Park Memorial Institute, RPMI-1640 (supplemented with 10% fetal bovine serum (FBS) and antibiotics) at several incubation times (24, 48, and 96 h at 37 °C) were tested. After a careful optimization and analytical performance, the developed method allows to simultaneously study the oxidation process, leading to the release of ionic species, and the increase in the hydrodynamic volume of PtNPs, probably related to the formation of new biological entities (protein corona). The magnitude of both processes was found to be dependent on the tested cell culture media and incubation times. Dynamic light scattering (DLS) and high-resolution scanning electron microscopy (HR-SEM) were used as complementary techniques to study the important process of both soft and hard protein corona formation. The feasibility of the HPLC-ICP-TQ-MS to get relevant information for toxicological studies has been demonstrated and in light of our results, the influence of the cell culture media on the behavior of PtNPs should not be underestimated.


Assuntos
Nanopartículas Metálicas , Platina , Bioensaio , Técnicas de Cultura de Células , Cromatografia Líquida de Alta Pressão , Nanopartículas Metálicas/toxicidade , Platina/toxicidade
5.
Phys Chem Chem Phys ; 23(38): 21959-21971, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34569570

RESUMO

Cisplatin, (NH3)2PtCl2, has been known as a successful metal-based anticancer drug for more than half a century. Its analogue, Argplatin, arginine-linked cisplatin, (Arg)PtCl2, is being investigated because it exhibits reactivity towards DNA and RNA that differs from that of cisplatin. In order to understand the basis for its altered reactivity, the deprotonated and sodium cationized forms of Argplatin, [(Arg-H)PtCl2]- and [(Arg)PtCl2 + Na]+, are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy in the IR fingerprint and hydrogen-stretching regions. Complementary electronic structure calculations are performed using density functional theory approaches to characterize the stable structures of these complexes and to predict their infrared spectra. Comparison of the theoretical IR spectra predicted for various stable conformations of these Argplatin complexes to their measured IRMPD spectra enables determination of the binding mode(s) of Arg to the Pt metal center to be identified. Arginine is found to bind to Pt in a bidentate fashion to the backbone amino nitrogen and carboxylate oxygen atoms in both the [(Arg-H)PtCl2]- and [(Arg)PtCl2 + Na]+ complexes, the NO- binding mode. The neutral side chain of Arg also interacts with the Pt center to achieve additional stabilization in the [(Arg-H)PtCl2]- complex. In contrast, Na+ binds to both chlorido ligands in the [(Arg)PtCl2 + Na]+ complex and the protonated side chain of Arg is stabilized via hydrogen-bonding interactions with the carboxylate moiety. These findings are consistent with condensed-phase results, indicating that the NO- binding mode of arginine to Pt is preserved in the electrospray ionization process even under variable pH and ionic strength.


Assuntos
Antineoplásicos/química , Arginina/química , Cisplatino/química , Óxido Nítrico/química , Platina/química , Sítios de Ligação , Teoria da Densidade Funcional , Estrutura Molecular , Espectrofotometria Infravermelho
6.
World J Surg Oncol ; 19(1): 272, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507562

RESUMO

BACKGROUND: To evaluate whether the addition of taxanes to platinum and fluoropyrimidines in adjuvant chemotherapy would result in longer survival than platinum plus fluoropyrimidines in gastric cancer patients who received D2 gastrectomy. METHODS: Data of patients with gastric adenocarcinoma who received D2 gastrectomy and adjuvant chemotherapy with platinum plus fluoropyrimidines or taxanes, platinum plus fluoropyrimidines was retrospectively collected and analyzed. 1:1 Propensity score matching analysis was used to balance baseline characteristics between two groups. Survival curves were estimated using Kaplan-Meier method, and the differences were compared using the log-rank test. RESULTS: Four hundred twenty-five patients in the platinum plus fluoropyrimidines group and 177 patients in the taxanes, platinum plus fluoropyrimidines group were included into analysis. No statistical differences in disease-free survival and overall survival were observed between two groups. After propensity score matching, 172 couples of patients were matched, the baseline characteristics were balanced. The median disease-free survival were 15.8 months (95% CI, 9.3~22.4) in the platinum plus fluoropyrimidines group and 22.6 months (95% CI, 15.9~29.4) in the taxanes, platinum plus fluoropyrimidines group (HR = 0.63; 95% CI, 0.48~0.85; P = 0.002). The median overall survival was 25.4 months for patients in the platinum plus fluoropyrimidines group (95% CI, 19.4~31.3) and 33.8 months (95% CI, 23.5~44.2) for those in the taxanes, platinum plus fluoropyrimidines group (HR = 0.68; 95% CI, 0.53-0.87; log-rank test, P = 0.002). CONCLUSIONS: For gastric adenocarcinoma patients, the adjuvant triplet combination of taxanes, platinum, and fluoropyrimidines regimen after D2 gastrectomy was superior to platinum plus fluoropyrimidines regimen in disease-free survival as well as overall survival. TRIAL REGISTRATION: This project has been registered in the Chinese Clinical Trial Registry ( ChiCTR1800019978 ).


Assuntos
Platina , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Gastrectomia , Humanos , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxoides/uso terapêutico
7.
Analyst ; 146(20): 6270-6280, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34549734

RESUMO

We propose the fabrication of a novel ready-to-use electrochemical sensor based on a screen-printed graphene paste electrode (SPGrE) modified with platinum nanoparticles and coated with a molecularly imprinted polymer (PtNPs@MIP) for sensitive and cost-effective detection of paraquat (PQ) herbicide. Successive coating of the PtNPs surface with SiO2 and vinyl end-groups formed the PtNPs@MIP. Next, we terminated the vinyl groups with a molecularly imprinted polymer (MIP) shell. MIP was attached to the PtNPs cores using PQ as the template, methacrylic acid (MAA) as the monomer, ethylene glycol dimethacrylate (EGDMA) as the cross-linker, and 2,2'-azobisisobutyronitrile (AIBN) as the initiator. Coating the SPGrE surface with PtNPs@MIP furnished the PQ sensor. We studied the electrochemical mechanism of PQ on the MIP sensor using cyclic voltammetry (CV) experiments. The PQ oxidation current signal appears at -1.08 V and -0.71 V vs. Ag/AgCl using 0.1 M potassium sulfate solution. Quantitative analysis was performed by anodic stripping voltammetry (ASV) using a deposition potential of -1.4 V for 60 s and linear sweep voltammetric stripping. The MIP sensor provides linearity from 0.05 to 1000 µM (r2 = 0.999), with a lower detection limit of 0.02 µM (at -0.71 V). The compact imprinted sensor gave a highly sensitive and selective signal toward PQ. The ready-to-use MIP sensor can provide an alternative approach to the determination of paraquat residue on vegetables and fruits for food safety applications.


Assuntos
Grafite , Nanopartículas Metálicas , Impressão Molecular , Técnicas Eletroquímicas , Eletrodos , Polímeros Molecularmente Impressos , Paraquat , Platina , Dióxido de Silício
8.
Analyst ; 146(18): 5691-5703, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515701

RESUMO

Platinum(II) complexes are the most commonly used anticancer drugs and potential optical materials, but the detectability of Pt(II) complex-based probes is seldom reported. In our previous work, a tetradentate Pt(II) complex Pt-CHO was utilised as a 'turn-off' probe to detect ClO- and image cancer cells. However, the recognition mechanism has not been completely clarified and there are still doubts. In this work, three Pt(II) complexes, Pt-H, Pt-CHO and Pt-COOH, were developed to elucidate the mechanism of this class of complexes and refine their property studies. As a result, the UV-visible absorption and luminescence emission experiments, as well as the mass spectrum, proved that the oxidation of Pt(II) to Pt(IV) was the real reason for luminescence quenching, which has nothing to do with aldehyde groups. This first reported mechanism introduces a new type of ClO- probe based on Pt(II) complexes, thereby expanding the application fields of platinum complexes. Moreover, the quantum yield measurements, the effect of biomolecules and reversibility were studied to improve the properties of the probes. Theoretical calculations were used to gain an in-depth understanding of optical characteristics and related mechanisms. The cell imaging of RAW264.7 cells under endogenous ClO- proved the potential of the probes in bioimaging.


Assuntos
Ácido Hipocloroso , Luminescência , Oxirredução , Estresse Oxidativo , Platina
9.
J Neural Eng ; 18(5)2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34428753

RESUMO

Objective. Neural interfaces based on carbon fiber (CF) electrodes have demonstrated key positive attributes such as minimal foreign body response and mechanical strength to self-insert in brain tissue. However, carbon does not form a low impedance electrode interface with neural tissue. Electrodeposited platinum iridium (PtIr) has been used to improve electrode interface properties for metallic bioelectrodes.Approach. In this study, a PtIr electrodeposition process has been performed on CF microelectrode arrays to improve the interfacial properties of these arrays. We study the film morphology and composition as well as electrode durability and impedance.Results. A PtIr coating with a composition of 70% Pt, 30% Ir and a thickness of ∼400 nm was observed. Pt and Ir were evenly distributed within the film. Impedance was decreased by 89% @ 1 kHz. Accelerated soak testing in a heated (T= 50∘C) saline solution showed impedance increase (@ 1 kHz) of ∼12% after 36 days (89 equivalent) of soaking.


Assuntos
Irídio , Platina , Fibra de Carbono , Impedância Elétrica , Galvanoplastia , Microeletrodos
10.
J Neural Eng ; 18(5)2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34433150

RESUMO

Objective.Electrical measurement of the activity of individual neurons is a primary goal for many invasive neural electrodes. Making these 'single unit' measurements requires that we fabricate electrodes small enough so that only a few neurons contribute to the signal, but not so small that the impedance of the electrode creates overwhelming noise or signal attenuation. Thus, neuroelectrode design often must strike a balance between electrode size and electrode impedance, where the impedance is often assumed to scale linearly with electrode area.Approach and main results. Here we study how impedance scales with neural electrode area and find that the 1 kHz impedance of Pt electrodes (but not Au electrodes) transitions from scaling with area (r-2) to scaling with perimeter (r-1) when the electrode radius falls below 10µm. This effect can be explained by the transition from planar to spherical diffusion behavior previously reported for electrochemical microelectrodes.Significance.These results provide important intuition for designing small, single unit recording electrodes. Specifically, for materials where the impedance is dominated by a pseudo-capacitance that is associated with a diffusion limited process, the total impedance will scale with perimeter rather than area when the electrode size becomes comparable with the diffusion layer thickness. For Pt electrodes this transition occurs around 10µm radius electrodes. At even lower frequencies (1 Hz) impedance approaches a constant. This transition tor-1scaling implies that electrodes with a pseudo-capacitance can be made smaller than one might expect before thermal noise or voltage division limits the ability to acquire high-quality single-unit recordings.


Assuntos
Ouro , Platina , Impedância Elétrica , Eletrodos Implantados , Microeletrodos , Neurônios
11.
Int J Nanomedicine ; 16: 5551-5563, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34429599

RESUMO

Background: Type I diabetes occurs when the pancreas can only make limited or minimal insulin. Patients with type 1 diabetes need effective approaches to manage diabetes and maintain their blood-glucose concentration. Recently, continuous glucose monitoring (CGM) has been used to help control blood-glucose levels in patients with type 1 diabetes. Patients with type 2 diabetes may also benefit from CGM on multiple insulin injections, basal insulin, or sulfonylureas. Enzyme-free glucose detection in a neutral environment is the recent development trend of CGM. Materials and Methods: Pt/Au alloy electrodes for enzyme-free glucose detection in a neutral environment were formed by electrochemically depositing Pt/Au alloy on a thin polycarbonate (PC) membrane surface with a uniformly distributed micro-hemisphere array. The PC membranes were fabricated using semiconductor microelectromechanical manufacturing processes, precision micro-molding, and hot embossing. Amperometry was used to measure the glucose concentration in PBS (pH 7.4) and artificial human serum. Results: The Pt/Au nanoalloy electrode had excellent specificity for glucose detection, according to the experimental results. The device had a sensitivity of 2.82 µA mM-1 cm-2, a linear range of 1.39-13.9 mM, and a detection limit of 0.482 mM. Even though the complex interfering species in human blood can degrade the sensing signal, further experiments conducted in artificial serum confirmed the feasibility of the proposed Pt/Au nanoalloy electrode in clinical applications. Conclusion: The proposed Pt/Au nanoalloy electrode can catalyze glucose reactions in neutral solutions with enhancing sensing performance by the synergistic effect of bimetallic materials and increasing detection surface area. This novel glucose biosensor has advantages, such as technology foresight, good detection performance, and high mass production feasibility. Thus, the proposed neutral nonenzymatic glucose sensor can be further used in CGMs.


Assuntos
Técnicas Biossensoriais , Diabetes Mellitus Tipo 2 , Glicemia , Automonitorização da Glicemia , Eletrodos , Glucose , Ouro , Humanos , Nanoestruturas , Platina
12.
Eur J Med Chem ; 223: 113730, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34388483

RESUMO

Alterations in lipid metabolism, commonly disregarded in the past, have been accepted as a hallmark for cancer. Exploring cancer therapeutics that interrupt the lipid metabolic pathways by monotherapy or combination with conventional chemotherapy or immunotherapy is of great importance. Here we modified cisplatin with an FDA-approved hypolipidemic drug, bezafibrate (BEZ), via the well-established Pt(IV) strategy, affording two multi-functional Pt(IV) anticancer agents cis,cis,trans-[Pt(NH3)2Cl2(BEZ)(OH)] (CB) and cis,cis,trans-[Pt(NH3)2Cl2(BEZ)2] (CP) (BEZ = bezafibrate). The Pt(IV) prodrug CB exhibited an enhanced anticancer activity up to 187-fold greater than the clinical anticancer drug cisplatin. Both CB and CP had less toxicity to normal cells, showing higher efficacies and superior therapeutic indexes than cisplatin. Mechanism studies revealed that the bezafibrate-conjugated Pt(IV) complex CB, as a representative, could massively accumulate in A549 cells and genomic DNA, induce DNA damage, elevate intracellular ROS levels, perturb mitochondrial transmembrane potentials, activate the cellular metabolic sensor AMPK, and result in profound proliferation inhibition and apoptosis. Further cellular data also provided evidence that phosphorylation of AMPK, as a metabolic sensor, could suppress the downstream HMGB1, NF-κB, and VEGFA, which may contribute to the inhibition of angiogenesis and metastasis. Our study suggests that the antitumor action of CB and CP mechanistically distinct from the conventional platinum drugs and that functionalizing platinum-based agents with lipid-modulating agents may represent a novel practical strategy for cancer treatment.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Bezafibrato/química , Hipolipemiantes/química , Platina/química , Pró-Fármacos/química , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Dano ao DNA/efeitos dos fármacos , Regulação para Baixo , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pró-Fármacos/farmacologia , Transdução de Sinais/efeitos dos fármacos
13.
Biomater Sci ; 9(18): 6214-6226, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34357368

RESUMO

A new biosensor for detecting cancer involved sentinel lymph nodes has been developed via the electrochemical tracing of fatty acid oxidation as a distinct metabolism of malignant cells invading lymph nodes (LNs). The system included integrated platinum needle electrodes that were decorated by carbon nanotubes (as hydrophobic agents) through laser-assisted nanowelding. It was applied to record the dielectric spectroscopy data from LN contents via electrochemical impedance spectroscopy. The system was applied for dielectric spectroscopy of LN contents via electrochemical impedance approach. The reduced lipid content of involved LNs, due to fat metabolism by invasive cancer cells, would decrease the charge transfer resistance (RCT) of the LNs with respect to their normal counterparts. Multi-walled carbon nanotubes (MWCNTs) with superhydrophobic properties were used to enhance the interaction of Pt needle electrodes with the lipidic contents of lymph nodes. This is the first time that a fatty acid metabolism-based sensing approach has been introduced to detect involved LNs. Moreover, a novel electrode decorating method was applied to enhance the interfacial contact of this lipid detection probe (LDP). In order to avoid doubt about the biocompatibility of ferrocyanide, [Fe(CN)6]4- and ferricyanide, [Fe(CN)6]3-, a biocompatible injectable metal ion-based material, ferric carboxymaltose, was selected and applied as the electrolyte for the first time. Rabbit LNs were tested using the LDP in the animal model phase. The system was then used in vitro on 122 dissected human LNs in the operating room. Calibration of the results showed an excellent match between the dielectric response of the LDP (known as charge transfer resistance (RCT)) and the final pathological diagnoses. The LDP may have a promising future after further clinical investigations for intra-operative distinction between normal and cancerous LNs.


Assuntos
Técnicas Biossensoriais , Nanotubos de Carbono , Neoplasias , Animais , Técnicas Eletroquímicas , Eletrodos , Lasers , Linfonodos , Agulhas , Platina , Coelhos
14.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445690

RESUMO

Platinum coordination complexes have found wide applications as chemotherapeutic anticancer drugs in synchronous combination with radiation (chemoradiation) as well as precursors in focused electron beam induced deposition (FEBID) for nano-scale fabrication. In both applications, low-energy electrons (LEE) play an important role with regard to the fragmentation pathways. In the former case, the high-energy radiation applied creates an abundance of reactive photo- and secondary electrons that determine the reaction paths of the respective radiation sensitizers. In the latter case, low-energy secondary electrons determine the deposition chemistry. In this contribution, we present a combined experimental and theoretical study on the role of LEE interactions in the fragmentation of the Pt(II) coordination compound cis-PtBr2(CO)2. We discuss our results in conjunction with the widely used cancer therapeutic Pt(II) coordination compound cis-Pt(NH3)2Cl2 (cisplatin) and the carbonyl analog Pt(CO)2Cl2, and we show that efficient CO loss through dissociative electron attachment dominates the reactivity of these carbonyl complexes with low-energy electrons, while halogen loss through DEA dominates the reactivity of cis-Pt(NH3)2Cl2.


Assuntos
Brometos/química , Complexos de Coordenação/química , Compostos de Platina/química , Antineoplásicos/química , Brometos/farmacologia , Cisplatino/farmacologia , Elétrons , Platina , Compostos de Platina/farmacologia
15.
In Vivo ; 35(5): 2821-2829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410974

RESUMO

BACKGROUND/AIM: Standard chemotherapy for advanced urothelial carcinoma (UC) patients with moderate renal dysfunction has not yet been established. PATIENTS AND METHODS: We retrospectively assessed outcomes of patients with advanced UC who underwent first-line chemotherapy with full-/reduced-dose gemcitabine plus cisplatin (GC-f/GC-r) or full-/reduced-dose gemcitabine plus carboplatin (G-Car-f/G-Car-r) according to renal function. RESULTS: Seventy-eight patients were included in this study. The objective response rate was 42%, 30%, 42%, and 27% for the GC-f, GC-r, G-Car-f, and G-Car-r groups, respectively. For the GC-r and G-Car-f groups, the median progression-free survival and the median overall survival was 4.5 vs. 7.0 months (p=0.07) and 7.5 months vs. 12.0 months (p=0.124), respectively. Grade 3/4 thrombocytopenia occurred more frequently in the GC-r group than the G-Car-f group (80% vs. 38%, p=0.021). CONCLUSION: G-Car-f could be more beneficial than GC-r for patients with advanced UC who have moderate renal dysfunction.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/efeitos adversos , Humanos , Rim/fisiologia , Platina , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico
16.
In Vivo ; 35(5): 2869-2874, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410980

RESUMO

BACKGROUND/AIM: Despite the presence of a mixed response (MR) in patients with urothelial carcinoma (UC) who receive immune checkpoint inhibitors, the clinical outcome of these patient has not been reported. We evaluated the clinical outcome of MR to pembrolizumab for advanced UC. PATIENTS AND METHODS: Advanced UC patients who received pembrolizumab after platinum-based chemotherapy failure with measurable disease in multiple organs were retrospectively analyzed. RESULTS: Among 31 patients, MR [including progressive disease (PD)+complete response (CR) or partial response (PR)] was confirmed in 4 (12.9%). The median overall survival (OS) of the CR+PR (including CR+SD±PR), stable disease (SD), PD (including PD±SD) and MR groups was 16.0, 5.1, 5.4 and 4.3 months, respectively. There was no significant difference in the OS between the MR and CR+PR response groups (log-rank test, p=0.069). CONCLUSION: A mixed response to pembrolizumab in advanced UC was not uncommon. Despite the non-significant difference in the OS between the mixed and CR+PR response groups, the OS of the MR group tended to be similar to that of the SD and PD response groups.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição/tratamento farmacológico , Humanos , Platina , Estudos Retrospectivos
17.
Talanta ; 234: 122647, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364456

RESUMO

Nanozymes, as a new type of artificial enzyme, have recently become a research hotspot in the field of catalysis and biomedicine. However, the application of nanozyme is limited by catalytic activity changes of different substrates and low specificity. This work shows that citrate-capped platinum nanoparticles (Cit-PtNPs) exhibit stronger oxidase-like activity than other platinum nanozymes at different pH when 3-methyl-2-benzothiazolinonehydrazone hydrochloride (MBTH) and n-ethyl-n- (2-hydroxy-3-sulfopropyl)-m-toluidine sodium salt (TOOS) were used as chromogenic substrates. This phenomenon has important reference value for different nanozymes to choose chromogenic substrates in catalysis. In MBTH-TOOS chromogenic system, MBTH (-NH) radical is first produced during the reaction through catalytic oxidation of Cit-PtNPs, which reacts with TOOS to produce a colorless compound. The blue-purple quinoid dye was produced through the dismutation of the colorless compound. The catalytic mechanism of the oxidase-like activity of Cit-PtNPs is that two-electron reduction process and four-electron reduction process are simultaneously carried out in the catalytic process. Furthermore, to solve the problem of low specificity of metal nanozymes, protamine is designed as aggregation promoter of Cit-PtNPs and the specifichydrolysis substrate of trypsin. In this work, it can achieve one-step detection of trypsin by the boosting oxidase activity of Cit-PtNPs at pH8. The catalytic activity of Cit-PtNPs is proportional to the concentration of trypsin. The linear range for trypsin is 1.0-70.0 ngmL-1 and the limit of detection is measured to be 0.6 ngmL-1. This novel method has also been successfully applied to the detection of inhibitors and trypsin in urine samples.


Assuntos
Nanopartículas Metálicas , Platina , Catálise , Colorimetria , Oxirredutases , Sódio , Tripsina
18.
Talanta ; 234: 122675, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364475

RESUMO

Hepatitis B virus (HBV) infection is one of the global healthcare burdens, and its early diagnosis is crucial for the prevention of HBV-induced chronic hepatitis, liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although different detection approaches have been reported, most of these methods either rely on sophisticated machines or procedures, which limit their use particularly in the high endemic, developing countries. In this work, we report a dual-sensing nanoplatform built on noble metal-molybdenum disulfide (MoS2) nanohybrids, and this platform can detect the HBV DNA target through either fluorometric or colorimetric readouts. The design with the silver nanocluster (AgNC)-MoS2 nanohybrid enables multiplex fluorescent detection, while the HBV DNA-regulated growth of platinum nanoparticles (PtNPs) on the MoS2 nanosheets offers signal-on colorimetric detection. Both AgNC-MoS2 and PtNP-MoS2 nanohybrids show high sensitivity with pico-molar detection limit and single nucleotide specificity, even with the spiked human serum. Collectively, the proposed nanohybrids possess their potential in the use of early HBV diagnosis, particularly suitable for the high endemic areas with limited medical and instrumental supports.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Colorimetria , DNA , Dissulfetos , Vírus da Hepatite B/genética , Humanos , Limite de Detecção , Molibdênio , Platina
19.
Talanta ; 234: 122699, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364495

RESUMO

Hydroperoxides play important roles in atmospheric chemical processes since they act as strong oxidants. This paper details with the modification, characterization and performance of different carbon-based screen-printed electrodes to develop a sensor that allows to analyze organic and inorganic hydroperoxides in atmospheric samples. Commercial electrodes made up of graphite, graphene, carbon nanotubes and graphene oxide were electrochemically activated and subsequently modified by layer-by-layer method with a conducting polymer of azure-A and electrodeposited platinum nanoparticles. Characterization of modified electrodes was performed by FE-SEM, XPS, Raman spectroscopy, cyclic voltammetry, and impedance spectroscopy. Even though all modified carbonaceous substrates enabled the development of competitive electrochemical sensors for (in)organic hydroperoxides detection, carbon nanotubes underlying substrate exhibited the best performances in terms of sensitivity, stability, limit of detection and linear range. This amperometric sensor displayed linear responses to hydroperoxides over 0.081-450 µM with detection limits in the range of 24-558 nM and sensitivity values among 0.0628±1.6E-4 and 0.0112±0.71E-4 µA/µM for the different hydroperoxides herein studied. The developed electrochemical sensor was successfully applied to the analysis of (in)organic hydroperoxides in rainwater samples. Measurements in rainwater were performed in a city located in the East of Spain and collected at two different sites (downtown and suburban area) on two different dates (July and November 2020). The presented results demonstrated high sensitivity and selectivity for the detection of hydroperoxides among a plethora of substances naturally present in rainwater.


Assuntos
Grafite , Nanopartículas Metálicas , Nanotubos de Carbono , Técnicas Eletroquímicas , Eletrodos , Peróxido de Hidrogênio , Limite de Detecção , Platina
20.
Medicine (Baltimore) ; 100(30): e26547, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397686

RESUMO

ABSTRACT: The main purpose of this study was to investigate current state of constipation for lung cancer (LC) patients receiving platinum-based chemotherapy. The relationships between social demography, clinical variables, psychological status, and constipation were analyzed. In addition, quality of life (QoL) in LC patients with constipation was also analyzed. One hundred LC patients participated in this cross-sectional study. Under the guidance of the researchers, Functional Living Index-Emesis, Piper Fatigue Scale, Patient Health Questionnaire, Generalized Anxiety Disorder-7, European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0), Pittsburgh Sleep Quality Index, General Well-being Scale, Social Support Rate Scale, General Self-Efficacy Scale, and other related questionnaires were completed. The result showed the symptom of constipation was observed in 41 (41%) LC patients. The occurrence and development of constipation were associated with gender, food intake, exercise, nausea, fatigue, anxiety, depression, sleep disorders, and happiness. The study also found patients with constipation had significant lower QoL scores, especially the score in the general state. Constipation was very common in LC patients undergoing platinum-based chemotherapy. Reduced food intake and fatigue were the independent factors. Constipation significantly affects the QoL of the patients. Therefore, more attention should be paid to the risk factors of constipation in LC patients undergoing platinum-based chemotherapy, the earlier intervention was done to these patients, the better to improve their QoL.


Assuntos
Constipação Intestinal/complicações , Platina/farmacologia , Qualidade de Vida/psicologia , Idoso , Constipação Intestinal/etiologia , Constipação Intestinal/psicologia , Estudos Transversais , Tratamento Farmacológico/métodos , Tratamento Farmacológico/estatística & dados numéricos , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/psicologia , Masculino , Pessoa de Meia-Idade , Questionário de Saúde do Paciente/estatística & dados numéricos , Platina/uso terapêutico
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