in vitro reactivity of the antineoplastic drug carmustin and acrolein with model peptides

The function of acetylcholinesterase (AChE) is the rapid hydrolysis of the neurotransmitter acetylcholine (ACh), which is involved in the numerous cholinergic pathways in both the central and the peripheral nervous system. Therefore, AChE measurement is of high value for therapy management, especially during the course of intoxication with different chemicals or drugs that inhibit the enzyme. Pyridinium or bispyridinium aldoximes (oximes) are able to recover the activity of the inhibited enzyme. Since their adverse effects are not well elucidated, in this study the efficiency of HI-6 oxime in protection and/or reactivation of human erythrocyte AChE inhibited by the antineoplastic drug irinotecan as well as its cyto/genotoxicity in vitro were investigated. HI-6 was effective in protection of AChE and increased its activity up to 30%; the residual activity after irinotecan inhibition was 7%. Also, it reactivated the enzyme previously inhibited by 50% irinotecan (4.6 microg/ml) applied at 1/4 of the IC50 value. The tested concentrations of HI-6 exhibited acceptable genotoxicity towards white blood cells, as estimated by the alkaline comet assay, DNA diffusion assay and cytogenetic endpoints (structural chromosome aberrations and cytokinesis-block micronucleus assay). The results obtained warrant the further investigation of HI-6 in vivo, as well as its development for possible application in chemotherapy.

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Formulation and in vitro evaluation of antineoplastic drug loaded nanoparticles as drug delivery system

African Journal of Pharmacy and Pharmacology ◽

10.5897/ajpp2013.3436 ◽

2013 ◽

Vol 7 (23) ◽

pp. 1592-1604 ◽

Cited By ~ 4

Author(s):

Dastagiri Reddy

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Antineoplastic Drug ◽

In Vitro Evaluation

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Highly Specific Prediction of Antineoplastic Drug Resistance With an In Vitro Assay Using Suprapharmacologic Drug Exposures

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/82.7.582 ◽

1990 ◽

Vol 82 (7) ◽

pp. 582-588 ◽

Cited By ~ 122

Author(s):

D. H. Kern ◽

L. M. Weisenthal

Keyword(s):

Drug Resistance ◽

In Vitro Assay ◽

Antineoplastic Drug ◽

Vitro Assay ◽

Specific Prediction ◽

Antineoplastic Drug Resistance

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The effect of size, charge and cyclization of model peptides on their in vitro release from dl–PLGA microspheres

Journal of Controlled Release ◽

10.1016/s0168-3659(97)00065-5 ◽

1997 ◽

Vol 49 (2-3) ◽

pp. 133-140 ◽

Cited By ~ 9

Author(s):

Franklin W Okumu ◽

Jeffrey L Cleland ◽

Ronald T Borchardt

Keyword(s):

In Vitro Release ◽

Plga Microspheres ◽

Vitro Release ◽

Model Peptides

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Quantitative Prediction of Oral Bioavailability of a Lipophilic Antineoplastic Drug Bexarotene Administered in Lipidic Formulation Using a Combined In Vitro Lipolysis/Microsomal Metabolism Approach

Journal of Pharmaceutical Sciences ◽

10.1016/j.xphs.2018.09.025 ◽

2019 ◽

Vol 108 (2) ◽

pp. 1047-1052 ◽

Cited By ~ 2

Author(s):

Jong Bong Lee ◽

Tae Hwan Kim ◽

Wanshan Feng ◽

Hyeon Gwan Choi ◽

Atheer Zgair ◽

...

Keyword(s):

Oral Bioavailability ◽

Antineoplastic Drug ◽

Quantitative Prediction ◽

Microsomal Metabolism ◽

In Vitro Lipolysis

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COXEN prediction of antineoplastic drug sensitivity in bladder cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.365 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 365-365

Author(s):

Shalin Kothari ◽

Daniel Gustafson ◽

Keith Killian ◽

James Costello ◽

Daniel C. Edelman ◽

...

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Gene Expression Data ◽

Drug Sensitivity ◽

Model Building ◽

Response To Therapy ◽

Antineoplastic Drug ◽

In Vitro Assays ◽

Expression Data

365 Background: COXEN (Co-eXpression ExtrapolatioN) uses molecular profiles as a “rosetta stone” for translating drug sensitivities of one set of cancers into predictions for another completely independent set of cell lines or human tumors. The ability of COXEN to predict drug effectiveness in pts using tumor samples from in vitro assays is unique. Methods: We tested the predictive value of COXEN for standard chemotherapies in a cohort of bladder cancer pts. Total RNA was extracted from formalin fixed paraffin embedded (FFPE) tissue and converted to cDNA, amplified with Ovation FFPE WTA, and hybridized to a GeneChip Human Genome U133 Plus 2.0 array. Using gene expression data from 278 independent bladder tumors, COXEN scores were generated using bioinformatics models originally built using the NCI-60 cell line panel and a model building algorithm (MiPP). Gene expression data was processed to score 76 FDA approved antineoplastic drugs. Results: A total of 24 samples were tested (15 tumors with 1 sample and 9 tumors with 2 biological replicas (2 samples from the same tumor)) from 15 pts who received chemotherapy (median age 64 (41-74); 73% male; with muscle invasive bladder cancer (MIBC) (12/15, 80%) or metastatic bladder cancer (mBC) (3/15, 20%)). Response to therapy was confirmed by pathologic response in MIBC pts and radiologic response in mBC pts. Chemotherapies evaluated included: methotrexate/vinblastine/doxorubicin/cisplatin; gemcitabine/cisplatin; gemcitabine/carboplatin; and cisplatin/etoposide. COXEN accurately predicted antineoplastic drug sensitivity in 11/15 (73%) pts (75% MIBC and 67% mBC), of which 7/11 pts had 2 biological samples. However, only 3/7 (43%) biological replicas confirmed COXEN prediction. COXEN accurately predicted drug sensitivity in 9/10 (90%) pts with response and 2/5 (40%) pts with resistance to therapy. Conclusions: COXEN did well in predicting antineoplastic drug response for the majority of bladder cancer pts in this cohort. However, predictions from 2 samples within the same tumor were not always consistent, likely due to the expected tumor heterogeneity found in bladder cancer tumors. A prospective clinical trial in patients with mBC using COXEN to select next best therapy is in development.

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