scholarly journals The Preparation, Determination of a Flexible Complex Liposome Co-Loaded with Cabazitaxel and β-Elemene, and Animal Pharmacodynamics on Paclitaxel-Resistant Lung Adenocarcinoma

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1697 ◽  
Author(s):  
Yi-Ying Zeng ◽  
Yi-Jun Zeng ◽  
Na-Na Zhang ◽  
Chen-Xi Li ◽  
Tian Xie ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Lung Adenocarcinoma ◽  
Malignant Tumors ◽  
Clinical Applications ◽  
Paclitaxel Resistance ◽  
Release Rates ◽  
Dialysis Method ◽  
Difficult Challenge ◽  
Weibull Equation

Paclitaxel is highly effective at killing many malignant tumors; however, the development of drug resistance is common in clinical applications. The issue of overcoming paclitaxel resistance is a difficult challenge at present. In this study, we developed nano drugs to treat paclitaxel-resistant lung adenocarcinoma. We selected cabazitaxel and β-elemene, which have fewer issues with drug resistance, and successfully prepared cabazitaxel liposome, β-elemene liposome and cabazitaxel-β-elemene complex liposome with good flexibility. The encapsulation efficiencies of cabazitaxel and β-elemene in these liposomes were detected by precipitation microfiltration and microfiltration centrifugation methods, respectively. Their encapsulation efficiencies were all above 95%. The release rates were detected by a dialysis method. The release profiles of cabazitaxel and β-elemene in these liposomes conformed to the Weibull equation. The release of cabazitaxel and β-elemene in the complex liposome were almost synchronous. The pharmacodynamics study showed that cabazitaxel flexible liposome and β-elemene flexible liposome were relatively good at overcoming paclitaxel resistance on paclitaxel-resistant lung adenocarcinoma. As the flexible complex liposome, the dosage of cabazitaxel could be reduced to 25% that of the cabazitaxel injection while retaining a similar therapeutic effect. It showed that β-elemene can replace some of the cabazitaxel, allowing the dosage of cabazitaxel to be reduced, thereby reducing the drug toxicity.

scholarly journals Histone demethylase KDM5A enhances cell proliferation, induces EMT in lung adenocarcinoma cells, and have a strong causal association with paclitaxel resistance

2021 ◽  
Author(s):  
Lidong Xu ◽  
Hong Wu ◽  
Xun Hu
Keyword(s):  
Cell Proliferation ◽  
Drug Resistance ◽  
Lung Adenocarcinoma ◽  
A549 Cells ◽  
Histone Demethylase ◽  
Causal Association ◽  
Paclitaxel Resistance ◽  
Mesenchymal Transition ◽  
Paclitaxel Treatment

Recent reports suggest that histone demethylase KDM5A emerges as a new player in the development of drug resistance and thus increases the challenges of chemotherapy. Here, we explore the role of KDM5A in cell proliferation, epithelial-mesenchymal transition (EMT)and its causal association with paclitaxel resistance in lung adenocarcinoma. Paclitaxel-resistant lung adenocarcinoma PTX-Calu-3 cells showed significantly higher IC50 value (7±0.176 µM) upon paclitaxel treatment than lung adenocarcinoma SK-LI-1 (3.6±0.005 nM), Calu-3 (4.3±0.015 nM), and A549 (4.5±0.106 nM) cells. We found that expression of KDM5A and P-glycoprotein (P-gp), which plays a critical role in the development of paclitaxel resistance, were significantly higher in PTX-Calu-3 cells compared to SK-LI-1, Calu-3, and A549 cells.. We observed a significant increase in the expression of mesenchymal markers N-cadherin and vimentin, and a concomitant decrease in expression of E-cadherin and α-catenin in PTX-Calu-3 compared to SK-LI-1, Calu-3, and A549 lung cancer cell lines. Transwell Boyden chamber and wound healing assays further demonstrated that a significantly higher number of PTX-Calu-3 cells were invasive and motile compared to SK-LI-1, Calu-3, and A549 cells, thus supporting the role of KDM5A in metastasis-associated processes. Additionally, a significantly higher expression of KDM5A was observed in lung adenocarcinoma patients’ samples compared with adjacent normal tissues as well as in PTX-Calu-3 cells compared toSK-LI-1, Calu-3, and A549 cells, as shown both with histochemistry and real time-polymerase chain reaction (RT-PCR). In summary, these results suggest that KDM5A plays a key role in lung adenocarcinoma by promoting proliferation, EMT, and drug resistance to paclitaxel treatment.

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

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.

The Frequency of HIV-1 Infection in Iranian Children and Determination of the Transmitted Drug Resistance in Treatment-Naïve Children

2020 ◽  
Vol 17 (6) ◽  
pp. 397-407
Author(s):  
Maryam Jarchi ◽  
Farah Bokharaei-Salim ◽  
Maryam Esghaei ◽  
Seyed Jalal Kiani ◽  
Fatemeh Jahanbakhsh ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Pediatric Patients ◽  
Phylogenetic Analyses ◽  
Rna Extraction ◽  
Transmitted Drug Resistance ◽  
The Arts ◽  
Treatment Naïve ◽  
Iranian Children ◽  
Hiv 1

Background: The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs. Objective: In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated. Materials: From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database. Results: Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children. Conclusion: The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.

Clinical applications of circulating tumor DNA in monitoring breast cancer drug resistance

2020 ◽  
Vol 16 (34) ◽  
pp. 2863-2878
Author(s):  
Yang Liu ◽  
Qian Du ◽  
Dan Sun ◽  
Ruiying Han ◽  
Mengmeng Teng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Clinical Applications ◽  
Current Status ◽  
Cancer Drug ◽  
Genomic Alteration ◽  
Tumor Dna

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. Unfortunately, treatments often fail because of the development of drug resistance, the underlying mechanisms of which remain unclear. Circulating tumor DNA (ctDNA) is free DNA released into the blood by necrosis, apoptosis or direct secretion by tumor cells. In contrast to repeated, highly invasive tumor biopsies, ctDNA reflects all molecular alterations of tumors dynamically and captures both spatial and temporal tumor heterogeneity. Highly sensitive technologies, including personalized digital PCR and deep sequencing, make it possible to monitor response to therapies, predict drug resistance and tailor treatment regimens by identifying the genomic alteration profile of ctDNA, thereby achieving precision medicine. This review focuses on the current status of ctDNA biology, the technologies used to detect ctDNA and the potential clinical applications of identifying drug resistance mechanisms by detecting tumor-specific genomic alterations in breast cancer.

Cisplatin Resistance Reversal of Lung Cancers by Tumor Acidity-Activable Vesicular Nanoreactors via Tumor Oxidative Stress Amplification

2021 ◽  
Author(s):  
Jean Felix Mukerabigwi ◽  
Yu Han ◽  
Nannan Lu ◽  
Wendong Ke ◽  
Yuheng Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Therapeutic Efficacy ◽  
Cisplatin Resistance ◽  
Clinical Applications ◽  
Lung Cancers ◽  
Resistance Reversal ◽  
Tumor Acidity ◽  
Stress Amplification ◽  
Novel Strategy

Drug resistance of cisplatin significantly limits its therapeutic efficacy in clinical applications against a variety of cancers. Herein, we develop a novel strategy to overcome cisplatin drug resistance through sensitizing...

scholarly journals Evaluation of free and total L-thyroxine in serum by a commercial procedure.

1981 ◽  
Vol 27 (1) ◽  
pp. 149-152 ◽  
Author(s):  
M J Obregon ◽  
A Kurtz ◽  
R Ekins ◽  
G Morreale de Escobar
Keyword(s):  
Pregnant Women ◽  
Plasma Proteins ◽  
Diagnostic Value ◽  
Free Thyroxine ◽  
Total Thyroxine ◽  
Dialysis Method ◽  
Hypothyroid Patients ◽  
Hyperthyroid Patients ◽  
Normal Controls

Abstract We assessed a commercial kit (Corning Medical) for "free" and total thyroxine determination, results being compared to those obtained by the Ekins and Ellis dialysis method (free thyroxine) and the method of Weeke and Orskov (total thyroxine). The kit procedure permits determination of both free and total thyroxine within 4 to 5 h, and the combined results may disclose changes in binding to plasma proteins that would be missed if only free thyroxine were determined. With both free-thyroxine methods, the values distinguished hyperthyroid patients from normal controls and pregnant women with 100% accuracy, but there was some overlap between hypothyroid patients and controls. Absolute values with the kit procedure often exceed those obtained by dialysis, especially for hypothyroid patients and pregnant women. We conclude that the kit may be of as much diagnostic value as the dialysis method if the limitations regarding absolute values are kept in mind and the test is not used as a substitute for thyrotropin determinations in cases of suspected hypothyroidism.

scholarly journals Determination of Drug Resistance and Virus Typology in HIV-1-Positive Pediatric Patients in Istanbul, Turkey

Intervirology ◽  
2014 ◽  
Vol 57 (5) ◽  
pp. 297-299 ◽  
Author(s):  
Özlem Yoldaş ◽  
Ali Ağaçfidan ◽  
Nadine Lübke ◽  
Ayper Somer ◽  
Selda Hançerli ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Pediatric Patients ◽  
Hiv 1

The determination of urea in soil extracts and related samples—a review

Soil Research ◽  
2004 ◽  
Vol 42 (7) ◽  
pp. 709 ◽  
Author(s):  
David F. Lambert ◽  
John E. Sherwood ◽  
Paul S. Francis
Keyword(s):  
Enzymatic Hydrolysis ◽  
Flow Injection Analysis ◽  
Acidic Solution ◽  
Clinical Applications ◽  
Urease Inhibitors ◽  
Viable Option ◽  
Soil Extracts ◽  
Diacetyl Monoxime ◽  
Hydrolysis Of

Although the dominant methods for the determination of urea in clinical applications incorporate selective enzymatic hydrolysis of urea, the determination of urea in soil extracts is complicated by the presence of urease inhibitors. The spectrophotometric determination of urea with an acidic solution diacetyl monoxime and semicarbazide is a viable option but traditional manual procedures are time-consuming. New variations on these procedures, based on microplates or flow-injection analysis methodologies, allow a far greater number of samples to be analysed with high precision and sensitivity.

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