Modulation of 5-fluorouracil host-toxicity and chemotherapeutic efficacy against human colon tumors by 5-(Phenylthio)acyclouridine, a uridine phosphorylase inhibitor

Cancer Chemotherapy and Pharmacology
O N Al SafarjalaniM H el Kouni

Abstract

The purpose of this investigation was to evaluate the effectiveness of oral 5-(phenylthio)acyclouridine (PTAU) in reducing 5-fluorouracil (FUra) host-toxicity and enhancing its chemotherapeutic efficacy against human colon tumors. PTAU is a potent and specific inhibitor of uridine phosphorylase (UrdPase, EC 2.4.2.3), the enzyme responsible for uridine catabolism. SCID mice bearing human colon DLD-1 or HCT-15 tumors were injected intraperitoneally with FUra (50, 200 or 300 mg/kg) on days 17, 24 and 31 after tumor cell inoculation. PTAU (120 mg/kg), uridine (1,320 mg/kg) or their combination was administered orally 2 or 4 h after FUra injection. Another four administrations of PTAU+uridine were given every 8 h after the first treatment with PTAU plus uridine. Survival and body weight were used to evaluate host toxicity. Tumor weight was used to evaluate the efficacy of the drugs on tumor growth. The mice were monitored for 38 days. Administration of the maximum tolerated dose (50 mg/kg) of FUra reduced DLD-1 and HCT-15 tumor weights by 48 and 59%, respectively, at day 38 post implantation. Administration of 200 mg/kg FUra resulted in 100% mortality. Oral administration of uridine (1,320 mg/kg) alone, 2 h following the administrat...Continue Reading

References

Mar 1, 1992·Journal of Hepatology·A HolstegeW Gerok
Jul 1, 1991·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G J Peters, C J van Groeningen
Mar 20, 1991·Journal of the National Cancer Institute·C J van GroeningenH M Pinedo
Jan 1, 1989·Pharmacology & Therapeutics·J W Darnowski, R E Handschumacher
Mar 1, 1986·The Journal of Pharmacy and Pharmacology·J C CradockS K Ackerman
Jan 18, 1989·Journal of the National Cancer Institute·C J van GroeningenH M Pinedo
Jul 1, 1988·Biochemical Pharmacology·J W Darnowski, R E Handschumacher
Jan 1, 1988·Cancer Chemotherapy and Pharmacology·T C ChanS B Howell
May 15, 1985·European Journal of Biochemistry·A HolstegeW Gerok
Jan 1, 1982·Cancer Chemotherapy and Pharmacology·P KlubesM A Meldon
Aug 14, 1981·Science·T GasserR E Handschumacher
Apr 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·D P KelsenJ Bertino
Jan 7, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M HidalgoE K Rowinsky
Aug 10, 2000·Biochemical Pharmacology·M H el KouniF N Naguib

❮ Previous
Next ❯

Citations

Mar 1, 2012·Cancer Chemotherapy and Pharmacology·Omar N Al SafarjalaniMahmoud H el Kouni
Sep 22, 2010·PloS One·Tarmo P Roosild, Samantha Castronovo
Aug 23, 2011·Journal of Structural Biology·Tarmo P RoosildGiuseppe Pizzorno
Jun 10, 2010·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Suleyman SalmanHalis Suleyman
Feb 6, 2018·Advanced Pharmaceutical Bulletin·Tahereh Eteraf-OskoueiMoslem Najafi
Nov 15, 2012·Clinical and Experimental Hypertension : CHE·Murat UnluKenan Sağlam
Jan 8, 2013·Clinical and Experimental Hypertension : CHE·Murat KaramanErgun Bozoglu

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.