The Molecular Aspect of Antitumor Effects of Protease Inhibitor Nafamostat Mesylate and Its Role in Potential Clinical Applications

Berberine is an isoquinoline alkaloid present in several plant species, including Coptis sp. and Berberis sp. In traditional medicine, extracts of berberine are used in the treatment of diarrhea of different origins. Recent studies have shown that berberine and its derivatives have significant biological effects on gastrointestinal (GI) and other functions and may become therapeutics for the treatment of diarrhea, gastroenteritis, diabetes, hyperlipidemia, cardiovascular diseases and inflammatory conditions. This paper summarizes the current knowledge on the actions of berberine in the GI tract. Binding and target sites, activated intracellular pathways, as well as the absorption and metabolism of berberine are discussed. Effects that may be useful in future clinical treatment, like antidiarrheal, anti-inflammatory and antitumor effects are critically reviewed and potential clinical applications are presented in detail.

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Chimeric Antigen Receptor-Modified T Cells for Solid Tumors: Challenges and Prospects

Journal of Immunology Research ◽

10.1155/2016/3850839 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 16

Author(s):

Yelei Guo ◽

Yao Wang ◽

Weidong Han

Keyword(s):

Solid Tumors ◽

Chimeric Antigen Receptor ◽

Antigen Receptor ◽

Outcome Data ◽

Clinical Applications ◽

Antitumor Effects ◽

Cell Based Therapy ◽

The Status ◽

Early Phase Clinical Trials

Recent studies have highlighted the successes of chimeric antigen receptor-modified T- (CART-) cell-based therapy for B-cell malignancies, and early phase clinical trials have been launched in recent years. The few published clinical studies of CART cells in solid tumors have addressed safety and feasibility, but the clinical outcome data are limited. Although antitumor effects were confirmedin vitroand in animal models, CART-cell-based therapy still faces several challenges when directed towards solid tumors, and it has been difficult to achieve the desired outcomes in clinical practice. Many studies have struggled to improve the clinical responses to and benefits of CART-cell treatment of solid tumors. In this review, the status quo of CART cells and their clinical applications for solid tumors will be summarized first. Importantly, we will suggest improvements that could increase the therapeutic effectiveness of CART cells for solid tumors and their future clinical applications. These interventions will make treatment with CART cells an effective and routine therapy for solid tumors.

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Preparation and In Vitro and In Vivo Antitumor Effects of VEGF Targeting Micelles

Technology in Cancer Research & Treatment ◽

10.1177/1533033820957022 ◽

2020 ◽

Vol 19 ◽

pp. 153303382095702

Author(s):

Jing Chang ◽

Zhe Yang ◽

Junfeng Li ◽

Yufen Jin ◽

Yihang Gao ◽

...

Keyword(s):

Lung Cancer ◽

Mouse Model ◽

Drug Loading ◽

Clinical Applications ◽

Loading Capacity ◽

Antitumor Effects ◽

Nude Mouse Model ◽

Targeting Ability

Background: Doxorubicin (DOX) has antitumor effects mediated by cell viability inhibition and by inducing cellular apoptosis. However, it has limited use in clinical applications due to various factors such as hydrophobicity, dose-dependent toxicity effects on normal tissues, short cycle retention time, and low targeting ability. This study aims at enhancing hydrophilicity of DOX to restrict its toxic effects to within or around the tumor sites and also to improve its targeting ability to enhance antitumor efficiency. Methods: Micelles composed of biodegradable poly (ethylene glycol)-poly (lactic acid) copolymers (PEG-PLA) were employed to deliver DOX via a self-assembly method and were coupled to VEGF antibodies. The morphology, size, and physical stability of PEG-PLA-DOX targeting VEGF micelles (VEGF-PEG-PLA-DOX micelles) were assessed. Then, the release ability of DOX from these micelles was monitored, and their drug loading capacity was calculated. MTT assay revealed the in vitro antitumor effect of VEGF-PEG-PLA-DOX micelles. Moreover, ROS release was measured to evaluate apoptotic effects of these nanoparticle micelles. In vivo therapeutic efficiencies of VEGF-PEG-PLA-DOX micelles on a lung cancer nude mouse model was evaluated. Results: DOX-loaded micelles were obtained with a drug loading capacity of 12.2% and were monodisperse with 220 nm average diameter and a controlled in vitro DOX release for extended periods. In addition, VEGF-PEG-PLA-DOX micelles displayed a larger cell viability inhibitory effect as measured via MTT assays and greater cell apoptosis induction through in vitro ROS levels compared with PEG-PLA-DOX micelles or free DOX. Furthermore, VEGF-PEG-PLA-DOX micelles could improve in vivo antitumor effects of DOX by reducing tumor volume and weight. Conclusions: VEGF-PEG-PLA-DOX micelles displayed a larger anti-tumor effect both in in vitro A549 cells and in an in vivo lung cancer nude mouse model compared with PEG-PLA-DOX micelles or free DOX, and hence they have potential clinical applications in human lung cancer therapy.

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Specimen Preparation for Clinical Applications of X-Ray Microanalysis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100135241 ◽

1990 ◽

Vol 48 (2) ◽

pp. 328-329

Author(s):

J.D. Shelburne ◽

G.M. Roomans

Keyword(s):

Carbon Coating ◽

Clinical Applications ◽

Point Of View ◽

Practical Significance ◽

Sweat Test ◽

Specimen Preparation ◽

Tissue Preparation ◽

X Ray ◽

Gallbladder Stones ◽

Clinical Problems

Proper preparative procedures are a prerequisite for the validity of the results of x-ray microanalysis of biological tissue. Clinical applications of x-ray microanalysis are often concerned with diagnostic problems and the results may have profound practical significance for the patient. From this point of view it is especially important that specimen preparation for clinical applications is carried out correctly.Some clinical problems require very little tissue preparation. Hair, nails, and kidney and gallbladder stones may be examined and analyzed after carbon coating. High levels of zinc or copper in hair may be indicative of dermatological or systemic diseases. Nail clippings may be analyzed (as an alternative to the more conventional sweat test) to confirm a diagnosis of cystic fibrosis. X-ray microanalysis in combination with scanning electron microscopy has been shown to be the most reliable method for the identification of the components of kidney or gallbladder stones.A quantitatively very important clinical application of x-ray microanalysis is the identification and quantification of asbestos and other exogenous particles in lung.

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Reduction of Potassium in Kidney Proximal Tubules to Aid in Electron Probe X-Ray Microanalysis of Calcium

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100119193 ◽

1985 ◽

Vol 43 ◽

pp. 474-475

Author(s):

A. LeFurgey ◽

P. Ingram ◽

L.J. Mandel

Keyword(s):

Smooth Muscle ◽

Proximal Tubule ◽

Electron Probe ◽

Clinical Applications ◽

Proximal Tubules ◽

Rabbit Kidney ◽

Target Cells ◽

X Ray ◽

Freeze Dried

For quantitative determination of subcellular Ca distribution by electron probe x-ray microanalysis, decreasing (and/or eliminating) the K content of the cell maximizes the ability to accurately separate the overlapping K Kß and Ca Kα peaks in the x-ray spectra. For example, rubidium has been effectively substituted for potassium in smooth muscle cells, thus giving an improvement in calcium measurements. Ouabain, a cardiac glycoside widely used in experimental and clinical applications, inhibits Na-K ATPase at the cell membrane and thus alters the cytoplasmic ion (Na,K) content of target cells. In epithelial cells primarily involved in active transport, such as the proximal tubule of the rabbit kidney, ouabain rapidly (t1/2= 2 mins) causes a decrease2 in intracellular K, but does not change intracellular total or free Ca for up to 30 mins. In the present study we have taken advantage of this effect of ouabain to determine the mitochondrial and cytoplasmic Ca content in freeze-dried cryosections of kidney proximal tubule by electron probe x-ray microanalysis.

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Simple teaching aid with clinical applications

Journal of Dental Education ◽

10.1002/j.0022-0337.1976.40.2.tb00939.x ◽

1976 ◽

Vol 40 (2) ◽

pp. 106-106

Author(s):

DL Torney ◽

HD Espinosa

Keyword(s):

Clinical Applications ◽

Teaching Aid

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Lexical Comprehension in Young Children With Developmental Delays

American Journal of Speech-Language Pathology ◽

10.1044/1058-0360.0301.79 ◽

1994 ◽

Vol 3 (1) ◽

pp. 79-88 ◽

Cited By ~ 1

Author(s):

Theresa A. Kouri

Keyword(s):

Young Children ◽

Developmental Delays ◽

Normal Development ◽

Clinical Applications ◽

Group Status ◽

Novel Object ◽

Related Information ◽

Comprehension Skills ◽

Lexical Items ◽

Lexical Concepts

Lexical comprehension skills were examined in 20 young children (aged 28–45 months) with developmental delays (DD) and 20 children (aged 19–34 months) with normal development (ND). Each was assigned to either a story-like script condition or a simple ostensive labeling condition in which the names of three novel object and action items were presented over two experimental sessions. During the experimental sessions, receptive knowledge of the lexical items was assessed through a series of target and generalization probes. Results indicated that all children, irrespective of group status, acquired more lexical concepts in the ostensive labeling condition than in the story narrative condition. Overall, both groups acquired more object than action words, although subjects with ND comprehended more action words than subjects with DD. More target than generalization items were also comprehended by both groups. It is concluded that young children’s comprehension of new lexical concepts is facilitated more by a context in which simple ostensive labels accompany the presentation of specific objects and actions than one in which objects and actions are surrounded by thematic and event-related information. Various clinical applications focusing on the lexical training of young children with DD are discussed.

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