It is generally assumed that drug concentration does not change significantly under cell culture conditions. Nevertheless, most of the therapeutic trials in acute leukemia that were based on in vitro drug sensitivity assays of patient samples have been disappointing. In order to show possible pitfalls of unphysiological alterations in vitro we investigated concentration versus time curves, metabolism and effects on the culture media for some antineoplastic drugs. Oxazaphosphorines and cytarabine were incubated in RPMI and in established cell lines and measured by HPLC. HPLC also served to measure enzyme activity and levels of related amino acids at various concentrations of asparaginase, ammonia release was photometrically determined. Etoposide was monitored by HPLC relative to different contents of FCS in RPMI. All oxazaphosphorines showed a rapid decrease of in vitro activity down to about 10% within 4-6 h, and 2% within 72 h. The level of cytarabine, when incubated in RPMI, was stable over 24h, and no change was seen with K562, while a rapid decrease to below 50% occurred within 6h in the presence of HL 60 and BLIN. 2 U/L of asparaginase led to asparagine depletion of the medium within 4h, while 200 U/L were associated with a preferential increase of glutamic acid and ammonia. Further, there was evidence of instability by rapid adsorption to plastic surfaces (paclitaxel) or isomerisation (etoposide) in RPMI with low FCS content. The instability of drugs in vitro is attributed to a variety of different factors: i.e. physico-chemical instability results in inactivation of oxazaphosphorines, cytarabine disappears by cellular metabolism without saturation depending on the cell-line. Epiphenomena like adsorption and isomerisation in vitro are unphysiological. Results of drug sensitivity assays should be interpreted with great caution.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1007/978-1-4615-4811-9_42 | DOI Listing |
Eur J Med Res
January 2025
Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China.
Objective: This study aimed to evaluate CTF1 expression in glioma, its relationship to patient prognosis and the tumor immune microenvironment, and effects on glioma phenotypes to identify a new therapeutic target for treating glioma precisely.
Methods: We initially assessed the expression of CTF1, a member of the IL-6 family, in glioma, using bioinformatics tools and publicly available databases. Furthermore, we examined the correlation between CTF1 expression and tumor prognosis, DNA methylation patterns, m6A-related genes, potential biological functions, the immune microenvironment, and genes associated with immune checkpoints.
Carbohydr Polym
March 2025
College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China. Electronic address:
Nobiletin (NOB), a lipid-soluble polymethoxyflavone with potent antioxidant, antimicrobial, and anti-inflammatory properties, suffers from poor stability and pH sensitivity, limiting its bioavailability. In this study, Pickering high internal phase emulsions (HIPEs) stabilized by soy protein isolate (SPI) and κ-carrageenan (KC) were developed to encapsulate and protect NOB. The emulsions, containing a 75 % medium-chain triglyceride (MCT) volume fraction, were optimized by investigating the effects of pH and KC concentration on the key properties such as the creaming index, particle size, zeta potential, microstructure, and rheology.
View Article and Find Full Text PDFCarbohydr Polym
March 2025
National Glycoengineering Research Center and Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, Shandong 266237, China; Suzhou Research Institute of Shandong University, Suzhou, Jiangsu 215123, China. Electronic address:
Camptothecin (CPT) exhibits potent anticancer activity, but its clinical application is limited by poor solubility and severe side effects. Hyaluronic acid (HA) is gaining attention in drug delivery systems due to its excellent biocompatibility and tumor-targeting properties. In this study, we conjugated CPT to the reducing end of ultra-low molecular weight HA to create a series of HA-decorated CPT conjugates.
View Article and Find Full Text PDFBiomaterials
January 2025
Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address:
Acute myeloid leukemia (AML) presents significant treatment challenges due to the severe toxicities and limited efficacy of conventional therapies, highlighting the urgency for innovative approaches. Organelle-targeting therapies offer a promising avenue to enhance therapeutic outcomes while minimizing adverse effects. Herein, inspired that primary AML cells are enriched with lysosomes and sensitive to lysosomophilic drugs (e.
View Article and Find Full Text PDFWorld J Gastroenterol
January 2025
Department of Spleen and Stomach Diseases, the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, Sichuan Province, China.
Background: Esophageal stricture ranks among the most significant complications following endoscopic submucosal dissection (ESD). Excessive fibrotic repair is a typical pathological feature leading to stenosis after ESD.
Aim: To examine the effectiveness and underlying mechanism of Kangfuxin solution (KFX) in mitigating excessive fibrotic repair of the esophagus post-ESD.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!