How Vital Are Patient-Reported Outcomes? Chang, Steven S; Movsas, Benjamin
JNCI : Journal of the National Cancer Institute,
03/2022, Letnik:
114, Številka:
3
Journal Article
Electrospun polyacrylonitrile (PAN) nanofiber membrane was functionalized with chitosan and proteins for use in the treatment of dye-containing wastewater. The PAN nanofiber membrane was subjected to ...alkaline hydrolysis, before being grafted with chitosan and subsequently the proteins from chicken egg white. The resultant nanofiber membrane (P-COOH-CS-CEW) was comprehensively characterized using thermogravimetric analysis, Fourier-transform infrared spectroscopy, and scanning electron microscopy. The efficiency of P-COOH-CS-CEW in removing cationic dye toluidine blue O (TBO) and anionic dye acid orange 7 (AO7) in aqueous solution was evaluated. Based on the performance of model fitting, Langmuir and pseudo-second-order kinetic model could be used to describe the performance of P-COOH-CS-CEW in the removal of TBO (pH 10) and AO7 (pH 2) from the dye solutions. The adsorbed TBO and AO7 dyes can be completely desorbed by an elution solution made of 50% (v/v) ethanol and 1 M sodium chloride. After five consecutive adsorption-desorption cycles, the efficiency of dye removal by P-COOH-CS-CEW was maintained above 97%.
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with no effective targeted therapy. Inducible nitric oxide synthase (iNOS) is associated with poor survival in patients ...with breast cancer by increasing tumor aggressiveness. This work aimed to investigate the potential of iNOS inhibitors as a targeted therapy for TNBC. We hypothesized that inhibition of endogenous iNOS would decrease TNBC aggressiveness by reducing tumor initiation and metastasis through modulation of epithelial-mesenchymal transition (EMT)-inducing factors.
iNOS protein levels were determined in 83 human TNBC tissues and correlated with clinical outcome. Proliferation, mammosphere-forming efficiency, migration, and EMT transcription factors were assessed in vitro after iNOS inhibition. Endogenous iNOS targeting was evaluated as a potential therapy in TNBC mouse models.
High endogenous iNOS expression was associated with worse prognosis in patients with TNBC by gene expression as well as immunohistochemical analysis. Selective iNOS (1400 W) and pan-NOS (L-NMMA and L-NAME) inhibitors diminished cell proliferation, cancer stem cell self-renewal, and cell migration in vitro, together with inhibition of EMT transcription factors (Snail, Slug, Twist1, and Zeb1). Impairment of hypoxia-inducible factor 1α, endoplasmic reticulum stress (IRE1α/XBP1), and the crosstalk between activating transcription factor 3/activating transcription factor 4 and transforming growth factor β was observed. iNOS inhibition significantly reduced tumor growth, the number of lung metastases, tumor initiation, and self-renewal.
Considering the effectiveness of L-NMMA in decreasing tumor growth and enhancing survival rate in TNBC, we propose a targeted therapeutic clinical trial by re-purposing the pan-NOS inhibitor L-NMMA, which has been extensively investigated for cardiogenic shock as an anti-cancer therapeutic.
For several decades, dinitrogen pentoxide (N
2
O
5
) has been recognized as an important reactive intermediate in the atmospheric chemistry of nitrogen oxides and nitrate aerosol, especially during ...nighttime. However, due to the lack of ambient observations of N
2
O
5
, the nocturnal nitrogen oxide chemistry could not be quantified until recent years. The objective of the present article is to assess the current state-of-the-art knowledge of N
2
O
5
dynamics within the tropospheric aerosol. An up-to-date summary of N
2
O
5
chemistry and major loss mechanisms are provided. Furthermore, techniques for measuring ambient N
2
O
5
and an overview of typical N
2
O
5
levels in the troposphere are described. In addition, model representations of N
2
O
5
chemistry are reviewed along with key features of N
2
O
5
vertical profiles based on numerical simulations. Lastly, the article provides the outstanding uncertainties and needs for further research into the atmospheric chemistry of N
2
O
5
. These include the need for better characterization of N
2
O
5
heterogeneous uptake under temperature conditions characteristic of mid- and high-latitude winter seasons; greater understanding of the influence of individual aerosol components on N
2
O
5
uptake and representation of these components in atmospheric models; and comprehensive descriptions of nighttime vertical profiles of N
2
O
5
and related pollutants.
Drugs that can treat one disease may either be detrimental or beneficial toward another due to possible cross-interactions. Therefore, care in choosing a suitable drug for patients with multiple ...diseases is crucial in successful patient management. This study explores several currently available ophthalmic drugs used to treat common ocular diseases to understand how they can affect the amyloidogenesis of a transforming growth factor β-induced protein (TGFBIp) peptide fragment found in abundance in the corneal protein aggregation deposits of lattice corneal dystrophy (LCD) patients. Results from this study provided supporting evidence that some drugs intended to treat other diseases can enhance or inhibit fibrillar aggregation of TGFBIp peptide, which may have potential implication of affecting the disease progression of LCD by either worsening or ameliorating it. Comparisons of the different properties of ophthalmic compounds explored in this study may also provide some guidance for future design of drugs geared toward the treatment of LCD.
Display omitted
•Aggregation of TGFBIp peptide fragment can be affected by various ocular drugs.•Drugs that induce or inhibit protein aggregation can promote or ameliorate disease.•Net charge, steric hindrance, and atomic interactions dictate peptide aggregation.
Display omitted
•A facile method of immobilizing RG19 dye on EDA-modified nanofiber membrane.•High DBC P-EDA-RG19 for lysozyme (769.23 mg/g).•P-EDA-RG19 is very selective in capturing lysozyme from ...complex feedstock.•Recovery yield and purification fold of lysozyme were 98.52% and 143, respectively.
The performance of lysozyme adsorption by the aminated nanofiber membrane immobilized with Reactive Green 19 (RG19) dyes was evaluated in batch and flow systems. The physicochemical properties of the dye-immobilized nanofiber membrane were characterized. The parameters of batch-mode adsorption of lysozyme (e.g., pH, initial dye concentration, and lysozyme concentration) were optimized using the Taguchi method. In a flow process, the factors influencing the dynamic binding performance for lysozyme adsorption in the chicken egg white (CEW) solution include immobilized dye concentration, adsorption pH value, feed flow rate, and feed CEW concentration. The impact of these operating conditions on the lysozyme purification process was investigated. Under optimal conditions, the recovery yield and purification factor of lysozyme achieved from the one-step adsorption process were 98.52% and 143 folds, respectively. The dye-affinity nanofiber membrane also did not exhibit any significant loss in its binding capacity and purification performance after five consecutive uses.
The proliferative and invasive nature of malignant cancers drives lethality. In glioblastoma, these two processes are presumed mutually exclusive and hence termed "go or grow." We identified a ...molecular target that shuttles between these disparate cellular processes-the molecular motor KIF11. Inhibition of KIF11 with a highly specific small-molecule inhibitor stopped the growth of the more treatment-resistant glioblastoma tumor-initiating cells (TICs, or cancer stem cells) as well as non-TICs and impeded tumor initiation and self-renewal of the TIC population. Targeting KIF11 also hit the other arm of the "go or grow" cell fate decision by reducing glioma cell invasion. Administration of a KIF11 inhibitor to mice bearing orthotopic glioblastoma prolonged their survival. In its role as a shared molecular regulator of cell growth and motility across intratumoral heterogeneity, KIF11 is a compelling therapeutic target for glioblastoma.
In this study, a polyacrylonitrile nanofiber membrane was first hydrolyzed and then functionalized with tris(hydroxymethyl)aminomethane (P-Tris), then used as an affinity nanofiber membrane for ...lysozyme adsorption in membrane chromatography. The dynamic adsorption behavior of lysozyme was investigated in a flow system under various operating parameters, including adsorption pHs, initial feed lysozyme concentration, loading flow rate, and the number of stacked membrane layers. Four different kinetic models, pseudo-first-order, pseudo-second-order, Elovich, and intraparticle diffusion kinetic models, were applied to experimental data from breakthrough curves of lysozyme. The results showed that the dynamic adsorption results were fitted well with the pseudo-second-order kinetic model. The breakthrough curve experimental results show significant differences in the breakthrough time, the dynamic binding capacity, the length of the mass transfer zone, and the utilization rate of the membrane bed under different operating parameters. Four dynamic adsorption models (i.e., Bohart–Adams, Thomas, Yoon–Nelson, and BDST models) were used to analyze the breakthrough curve characteristics of the dynamic adsorption experiments. Among them, the Yoon–Nelson model was the best model to fit the breakthrough curve. However, some of the theoretical results based on the Thomas and Bohart–Adams model analyses of the breakthrough curve fit well with the experimental data, with an error percentage of <5%. The Bohart–Adams model has the largest difference from the experimental results; hence it is not suitable for breakthrough curve analysis. These results significantly impact dynamic kinetics studies and breakthrough curve characteristic analysis in membrane bed chromatography.
PDF
