Toxicogenomics profiling of bone marrow from rats treated with topotecan in combination with oxaliplatin: a mechanistic strategy to inform combination toxicity

Frontiers in Genetics
Myrtle DavisPierre R Bushel

Abstract

Combinations of anticancer agents may have synergistic anti-tumor effects, but enhanced hematological toxicity often limit their clinical use. We examined whether "microarray profiles" could be used to compare early molecular responses following a single dose of agents administered individually with that of the agents administered in a combination. We compared the mRNA responses within bone marrow of Sprague-Dawley rats after a single 30 min treatment with topotecan at 4.7 mg/kg or oxaliplatin at 15 mg/kg alone to that of sequentially administered combination therapy or vehicle control for 1, 6, and 24 h. We also examined the histopathology of the bone marrow following all treatments. Drug-related histopathological lesions were limited to bone marrow hypocellularity for animals dosed with either agent alone or in combination. Lesions had an earlier onset and higher incidence for animals given topotecan alone or in combination with oxaliplatin. Severity increased from mild to moderate when topotecan was administered prior to oxaliplatin compared with administering oxaliplatin first. Notably, six patterns of co-expressed genes were detected at the 1 h time point that indicate regulatory expression of genes that are dependent on t...Continue Reading

References

Apr 3, 1998·Matrix Biology : Journal of the International Society for Matrix Biology·K Nagata
Apr 16, 1999·Molecular Carcinogenesis·E F NuwaysirC A Afshari
Dec 22, 1999·Seminars in Cell & Developmental Biology·S R Lamandé, J F Bateman
May 16, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M J de JongeJ Verweij
Jan 4, 2001·Current Biology : CB·L M Hendershot, N J Bulleid
Sep 19, 2001·Biochemistry·D G KakhniashviliS R Goodman
Dec 26, 2001·Nucleic Acids Research·Ron EdgarAlex E Lash
Apr 11, 2002·American Journal of Clinical Oncology·Jérôme AlexandreFrançois Goldwasser
May 9, 2002·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G TortoraA R Bianco
Dec 19, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lena E FribergMats O Karlsson
Feb 13, 2003·Nucleic Acids Research·Rafael A IrizarryTerence P Speed
Jul 8, 2003·The Journal of Pathology·Ruth Chiquet-Ehrismann, Matthias Chiquet
Jul 2, 2005·Toxicology and Applied Pharmacology·Stefan RueppSilvio Albertini
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jul 26, 2006·Bioinformatics·Yong WangLuonan Chen
Sep 26, 2006·Gynecologic Oncology·John C ElkasG Scott Rose
Nov 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·P R BushelR S Paules
Dec 25, 2007·Pharmacogenomics·Brigitte GanterAntoaneta Vladimirova
Jul 23, 2008·Current Genomics·Murty V ChengalvalaGregory S Kopf
Sep 2, 2008·Current Opinion in Pharmacology·Timothy P RyanCraig E Thomas
Sep 27, 2008·BMC Bioinformatics·Martijn P van IerselChris Evelo
Oct 20, 2009·Journal of Cell Communication and Signaling·Kim S Midwood, Gertraud Orend
Jun 5, 2010·Chemical Research in Toxicology·Hisham K HamadehCynthia A Afshari
Aug 3, 2010·The Pharmacogenomics Journal·J HuangP R Bushel
Oct 5, 2010·Toxicology and Applied Pharmacology·Heidrun Ellinger-ZiegelbauerAngela Mally
Oct 30, 2010·Nature Reviews. Drug Discovery·Shivanni KummarJames H Doroshow
Jul 30, 2011·Prehospital Emergency Care : Official Journal of the National Association of EMS Physicians and the National Association of State EMS Directors·UNKNOWN National Association of EMS Physicians
Sep 10, 2011·Oxidative Medicine and Cellular Longevity·Saleh A Bakheet
Nov 19, 2011·Nucleic Acids Research·Thomas KelderAlexander R Pico
May 5, 2012·Anti-cancer Drugs·Vivian E von GruenigenSteven E Waggoner
Nov 30, 2012·Nucleic Acids Research·Tanya BarrettAlexandra Soboleva

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE63902

Methods Mentioned

BETA
transcription profiling
chip
in vitro transcription
bone marrow collection
GTPase

Software Mentioned

Bioconductor
Bioconductor R package
Gene Set Enrichment Analysis ( GSEA )
2100 Expert
Expression Analysis
R
Pathway Studio
affyQCReport
pvac
Sub

Related Concepts

Related Feeds

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.

© 2022 Meta ULC. All rights reserved