A cDNA-microarray analysis of camptothecin resistance in glioblastoma cell lines

Morandi, Elena; Zingaretti, Chiara; Chiozzotto, Daniela; Severini, Cinzia; Semeria, Alessandro; Horn, Wolfango; Vaccari, Monica; Serra, Roberto; Silingardi, Paola; Colacci, Annamaria

doi:10.1016/j.canlet.2005.01.017

Cited by 17 publications

(12 citation statements)

References 32 publications

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“…[25][26][27] Resistance to irinotecan and SN-38 is likely mediated by production of IL-1 beta, with activation of NF-kB, a key transcriptional factor that inhibits the apoptotic response. 28,29 SN-38 is further metabolized in the liver to an inactive metabolite, SN-38 glucuronide. Inactivation and metabolism of SN-38 require uridine diphosphateglucuronosyltransferase 1A1 (UGT1A1), but an inheritable polymorphism of the gene for UGT1A1 is associated with reduced expression and a heightened risk of treatment-related toxicity, particularly severe diarrhea and neutropenia.…”

Section: Irinotecan: a New Therapeutic Optionmentioning

confidence: 99%

Experience with irinotecan for the treatment of malignant glioma

Vredenburgh¹,

Desjardins²,

Reardon³

et al. 2009

Neuro-Oncology

154

122

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Malignant glioma is the most commonly occurring primary malignant brain tumor. It is difficult to treat and is usually associated with an inexorable, rapidly fatal clinical course. Chemotherapy, radiotherapy, and surgical excision are core components in the management of malignant glioma. However, chemotherapy, even with the most active regimens currently available, achieves only modest improvement in overall survival. Novel agents and new approaches to therapy are required to improve clinical outcomes. Irinotecan, a first-line treatment for metastatic colorectal cancer and an agent with high activity against solid tumors of the gastrointestinal tract, is an inhibitor of topoisomerase I, a critical enzyme needed for DNA transcription. Irinotecan crosses the blood-brain barrier and, in preclinical investigations, has demonstrated cytotoxic activity against central nervous system tumor xenografts. Its antitumor activity has also been demonstrated against glioblastoma cells with multidrug resistance. Studies in adult and pediatric patients with recurrent, intractable malignant glioma have evaluated irinotecan as monotherapy and in combination with other agents, including temozolomide, carmustine, thalidomide, and bevacizumab. Studies of irinotecan in combination with other medications, particularly temozolomide and bevacizumab, have yielded promising results. Irinotecan monotherapy has demonstrated efficacy; however, its efficacy appears to be enhanced when used in combination with other chemotherapeutic agents. When administered concurrently with enzyme-inducing antiepileptic drugs, the dosage must be increased to compensate for enhanced cytochrome CY3A4/5 enzyme activity. Toxicities associated with irinotecan have been manageable; the most important dose-limiting toxicities are neutropenia and diarrhea. Irinotecan-based chemotherapy of malignant glioma merits further study.

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Section: Irinotecan: a New Therapeutic Optionmentioning

confidence: 99%

Experience with irinotecan for the treatment of malignant glioma

Vredenburgh¹,

Desjardins²,

Reardon³

et al. 2009

Neuro-Oncology

154

122

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“…For example, astrocytoma cells respond to treatment with IL-1␤ by up-regulating mRNAs encoding IL-1␣ or IL-1␤, IL-1R, and tumor necrosis factor ␣ mRNAs (9). Recent work reveals that this autocrine loop plays an important role in the development of resistance to the antitumor drug camptothecin, which induces the expression of IL-1␤ by activating NFB, inducing in turn the secretion of more IL-1␤ (10). The IL-1R is a member of the large IL-1R/Toll-like receptor (TLR) superfamily, which is defined by a conserved intracellular domain.…”

mentioning

confidence: 99%

Dose-dependent cross-talk between the transforming growth factor-β and interleukin-1 signaling pathways

Lü¹,

Tian²,

Han

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

101

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Some tumor cell lines secrete high concentrations of TGF␤ or IL-1. Similarly high concentrations of each of these cytokines cross-activate the other pathway: TGF␤ activates NFB, and IL-1␤ activates Smads. The IL-1 signaling components IRAK, MyD88, TRAF6, and TAK1 are all required for cross-activation of NFB by TGF␤. Knockdown experiments revealed that both TGF␤ receptor subunits are required for IL-1␤ to activate Smads, and the IL-1 receptor is required for TGF␤ to activate NFB. Coimmunoprecipitations showed that either TGF␤ or IL-1␤ stimulate ligand-dependent association of all three receptor subunits. Furthermore, cross-talk between the TGF␤ and IL-1 signaling pathways leads to dose-dependent cross-control of gene expression. These interactions provide new insight into biological responses to IL-1 and TGF␤ in the proximity of tumors that secrete high concentrations of these factors and probably also at sites of inflammation, where the local concentrations of these cytokines are likely to be high.cytokine receptors ͉ NFB ͉ Smad ͉ TLRs M embers of the TGF␤ superfamily regulate many developmental processes, and TGF␤ is involved in many human diseases, including cancer, where it functions, paradoxically, both as an antiproliferative factor and a tumor promoter (1). The TGF␤ receptor (T␤R) is a complex of two single-pass transmembrane subunits, T␤RI and T␤RII, which contain intracellular serine/ threonine kinase domains. Ligand binding induces T␤RI and T␤RII to associate, leading to the phosphorylation of T␤RI by T␤RII, activating its kinase domain. Activated T␤RI then phosphorylates and activates the transcription factors Smad 2 and Smad 3 (1, 2). TGF␤ can also activate other signaling proteins, including MAP kinases and, especially relevant to the work reported here, NFB (3, 4). The balance between Smad activation and other signals is likely to help determine whether TGF␤ suppresses or promotes cancer (1, 2).IL-1 plays a crucial role in inflammation, stress, and disease (5, 6). IL-1␣ or IL-1␤ bind to and activate the IL-1 receptor (IL-1R) (5). IL-1R and the adaptor protein myeloid differentiation factor 88 (MyD88) interact through their intracellular domains (5-7). The death domain of MyD88 then recruits the IL-1R-associated kinase (IRAK) to the receptor complex (5, 7). IRAK is phosphorylated, dissociates from the receptor complex, and recruits tumor necrosis factor ␣ receptor-associated factor 6 (TRAF6), which in turn activates the downstream kinase TGF␤ activating kinase 1 (TAK1), eventually leading to the activation of inhibitor of NFB (IB), the phosphorylation and degradation of IB, and the activation of NFB (5-8). Responses to IL-1 are amplified through an autocrine loop. For example, astrocytoma cells respond to treatment with IL-1␤ by up-regulating mRNAs encoding IL-1␣ or IL-1␤, IL-1R, and tumor necrosis factor ␣ mRNAs (9). Recent work reveals that this autocrine loop plays an important role in the development of resistance to the antitumor drug camptothecin, which induces the expression of IL-1␤ by activa...

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“…In addition to DNA repair genes, we have also detected genes involved in (i) chromatin and DNA metabolism, such as histone and ribonucleotide reductase genes; (ii) protein degradation, such as genes encoding ubiquitin and subunits of the proteasome; and (iii) signal transduction and cell cycle, such as polo-like kinase and calmodulin genes. Some of the genes observed to be more induced in the presence of CPT were also seen to be expressed in other studies addressing the global transcriptional regulation of genes by CPT-induced DNA damage (13,32,50,52,77). Genes that act in the ubiquitin/proteasome-dependent degradation pathway (77), in DNA repair (such as RAD51 and PARP) (52), and in chromatin architecture (such as the histone H2A gene) (50) were also detected as being more induced by CPT.…”

Section: Vol 5 2006mentioning

confidence: 62%

“…Some of the genes observed to be more induced in the presence of CPT were also seen to be expressed in other studies addressing the global transcriptional regulation of genes by CPT-induced DNA damage (13,32,50,52,77). Genes that act in the ubiquitin/proteasome-dependent degradation pathway (77), in DNA repair (such as RAD51 and PARP) (52), and in chromatin architecture (such as the histone H2A gene) (50) were also detected as being more induced by CPT. The participation of these genes in the CPT DNA damage transcriptional response remains to be determined.…”

Section: Vol 5 2006mentioning

confidence: 62%

Transcriptome Analysis of Aspergillus nidulans Exposed to Camptothecin-Induced DNA Damage

Malavazi¹,

Savoldi²,

Zingaretti

et al. 2006

Eukaryot Cell

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We have used an Aspergillus nidulans macroarray carrying sequences of 2,787 genes from this fungus to monitor gene expression of both wild-type and uvsB ATR (the homologue of the ATR gene) deletion mutant strains in a time course exposure to camptothecin (CPT). The results revealed a total of 1,512 and 1,700 genes in the wild-type and uvsB ATR deletion mutant strains that displayed a statistically significant difference at at least one experimental time point. We characterized six genes that have increased mRNA expression in the presence of CPT in the wild-type strain relative to the uvsB ATR mutant strain: fhdA (encoding a forkheadassociated domain protein), tprA (encoding a hypothetical protein that contains a tetratrico peptide repeat), mshA (encoding a MutS homologue involved in mismatch repair), phbA (encoding a prohibitin homologue), uvsC RAD51 (the homologue of the RAD51 gene), and cshA (encoding a homologue of the excision repair protein ERCC-6 [Cockayne's syndrome protein]). The induced transcript levels of these genes in the presence of CPT require uvsB ATR . These genes were deleted, and surprisingly, only the ⌬uvsC mutant strain was sensitive to CPT; however, the others displayed sensitivity to a range of DNA-damaging and oxidative stress agents. These results indicate that the selected genes when inactivated display very complex and heterogeneous sensitivity behavior during growth in the presence of agents that directly or indirectly cause DNA damage. Moreover, with the exception of UvsC, deletion of each of these genes partially suppressed the sensitivity of the ⌬uvsB strain to menadione and paraquat. Our results provide the first insight into the overall complexity of the response to DNA damage in filamentous fungi and suggest that multiple pathways may act in parallel to mediate DNA repair.

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A cDNA-microarray analysis of camptothecin resistance in glioblastoma cell lines

Cited by 17 publications

References 32 publications

Experience with irinotecan for the treatment of malignant glioma

Experience with irinotecan for the treatment of malignant glioma

Dose-dependent cross-talk between the transforming growth factor-β and interleukin-1 signaling pathways

Transcriptome Analysis of Aspergillus nidulans Exposed to Camptothecin-Induced DNA Damage

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