Prevalidation of a model for predicting acute neutropenia by colony forming unit granulocyte/macrophage (CFU-GM) assay

Pessina, Augusto; Albella, Beatriz; Bueren, Juan A.; Brantom, Paul; Casati, Silvana; Gribaldo, Laura; Croera, Cristina; Gagliardi, Gaetano; Foti, Paola; Parchment, Ralph E.; Parent‐Massin, D.; Sibiril, Y.; Heuvel, Rosette Van Den

doi:10.1016/s0887-2333(01)00085-6

Cited by 107 publications

(84 citation statements)

References 13 publications

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“…Human CFU-GM Assay Validation of the CFU-GM assay and IC 90 end points were described previously (19,20). To eliminate intersubject variation as a source of experimental variation, cells from the same donors were used throughout the study.…”

Section: Cfu-gm Colony Formation Assay To Determine Potentiation Of Mmentioning

confidence: 99%

“…To eliminate intersubject variation as a source of experimental variation, cells from the same donors were used throughout the study. Cells were thawed using a European Center for the Validation of Alternative Methods procedure (19,20), and cell number and viability were determined using trypan blue. Peripheral blood mononuclear cells (2.2 Â 10 6 /300 AL) were added to MethoCult H4001 (Stem Cell Technologies, Inc.), followed by addition of CEP-8983 (1 or 3 Amol/L) and topotecan or temozolomide, and cultures were plated and incubated in a humidified, 5% CO2/95% air environment at 37jC for 14 days.…”

Section: Cfu-gm Colony Formation Assay To Determine Potentiation Of Mmentioning

confidence: 99%

“…The end point of the assay for quantifying interspecies differences in susceptibility to drug toxicity is the IC 90 and is calculated based on log-linear regression data as detailed (European Center for the Validation of Alternative Methods, Ispra, Italy; refs. 12,14,15,19).…”

Section: Cfu-gm Colony Formation Assay To Determine Potentiation Of Mmentioning

confidence: 99%

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The selective poly(ADP-ribose) polymerase-1(2) inhibitor, CEP-8983, increases the sensitivity of chemoresistant tumor cells to temozolomide and irinotecan but does not potentiate myelotoxicity

Miknyoczki¹,

Chang²,

Grobelny³

et al. 2007

Molecular Cancer Therapeutics

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The effect of the potent and selective poly(ADP-ribose) (PAR) polymerase-1 [and PAR polymerase-2] inhibitor CEP-8983 on the ability to sensitize chemoresistant glioblastoma (RG2), rhabdomyosarcoma (RH18), neuroblastoma (NB1691), and colon carcinoma (HT29) tumor cells to temozolomide-and camptothecin-induced cytotoxicity, DNA damage, and G 2 -M arrest and on the potentiation of chemotherapy-induced myelotoxicity was evaluated using in vitro assays. In addition, the effect of the prodrug CEP-9722 in combination with temozolomide and/or irinotecan on PAR accumulation and tumor growth was also determined using glioblastoma and/or colon carcinoma xenografts relative to chemotherapy alone. CEP-8983 sensitized carcinoma cells to the growth-inhibitory effects of temozolomide and/or SN38 increased the fraction of and/ or lengthened duration of time tumor cells accumulated in chemotherapy-induced G 2 -M arrest and sensitized tumor cells to chemotherapy-induced DNA damage and apoptosis. A granulocyte-macrophage colony-forming unit colony formation assay showed that coincubation of CEP-8983 with temozolomide or topotecan did not potentiate chemotherapy-associated myelotoxicity. CEP-9722 (136 mg/kg) administered with temozolomide (68 mg/kg for 5 days) or irinotecan (10 mg/kg for 5 days) inhibited significantly the growth of RG2 tumors (60%) or HT29 tumors (80%) compared with temozolomide or irinotecan monotherapy, respectively. In addition, CEP-9722 showed ''stand alone'' antitumor efficacy in these preclinical xenografts. In vivo biochemical efficacy studies showed that CEP-9722 attenuated PAR accumulation in glioma xenografts in a dose-and time-related manner. These data indicate that CEP-8983 and its prodrug are effective chemosensitizing agents when administered in combination with select chemotherapeutic agents against chemoresistant tumors. [Mol Cancer Ther 2007;6(8):2290-302]

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Section: Cfu-gm Colony Formation Assay To Determine Potentiation Of Mmentioning

confidence: 99%

Section: Cfu-gm Colony Formation Assay To Determine Potentiation Of Mmentioning

confidence: 99%

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The selective poly(ADP-ribose) polymerase-1(2) inhibitor, CEP-8983, increases the sensitivity of chemoresistant tumor cells to temozolomide and irinotecan but does not potentiate myelotoxicity

Miknyoczki¹,

Chang²,

Grobelny³

et al. 2007

Molecular Cancer Therapeutics

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“…In vitro models of hematopoiesis are promising for determining hematotoxic effects (Deldar & Parchment, 1997;Du et al, 1990;Parent-Massin, 2001;Pessina et al, 2001;, 2010, even in the absence of information about the type of metabolism triggered in response to, and the target organ toxicity of, a test agent (Negro et al, 2001). Furthermore, these predictive in vitro assays have the potential to substantially reduce and refine animal usage, and could make possible human toxicology studies in preclinical settings (Gribaldo et al, 1998a,b;Pessina et al, 2001Pessina et al, , 2002Pessina et al, , 2010.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, these predictive in vitro assays have the potential to substantially reduce and refine animal usage, and could make possible human toxicology studies in preclinical settings (Gribaldo et al, 1998a,b;Pessina et al, 2001Pessina et al, , 2002Pessina et al, , 2010. The present study was designed to evaluate the potential effects of cypermethrin and mancozeb on hematopoiesis through lineage-specific colony formation in a clonogenic assay.…”

Section: Introductionmentioning

confidence: 99%

In vitromyelotoxic effects of cypermethrin and mancozeb on human hematopoietic progenitor cells

Mandarapu

Prakhya

2014

Journal of Immunotoxicology

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In the past two decades, hematologic and immunologic disorders in humans have been increasingly reported as a result of pesticide exposures. Therefore, safety assessment is required to assess the effects on hematopoiesis and thus on the immune system in addition to routine toxicity evaluation. Currently, the data available on effects of pesticides on hematopoiesis in humans is limited. In the study here, cypermethrin and mancozeb were evaluated for their possible effects on hematopoiesis in vitro. Hematopoietic stem or progenitor cells from human cord blood were isolated and then exposed for 14 days to cypermethrin or mancozeb at noncytotoxic doses (0.9-16 mM), and the effect on hematopoiesis screened via a methylcellulosebased clonogenic assay. Results indicated there were significant concentration-related decreases in clonogenic potentials of erythroid and granulocyte-macrophage colony formation. respectively. These data suggest that erythroid progenitors are perhaps more sensitive to these pesticides. Still, further studies are needed to understand the functional significance of these in vitro findings. For now, these data, albeit preliminary, emphasize the need to include an expanded battery of tests to understand effects on immune parameters in pre-clinical safety studies with pesticides. This study also emphasizes the utility of human cord blood in assessing potential effects on hematopoiesis in vitro.

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CFU‐GM Assay for Evaluation of Drug Myelotoxic Activity

Pessina

Bonomi

2007

CP Toxicology

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To study hematotoxicity of compounds on the myeloid cell compartment, the authors describe a standard procedure developed as a workable good laboratory practices-compliant protocol to determine the in vitro myelotoxic effect of drugs and chemicals. Specific protocols are presented to prepare human and murine myeloid progenitors (CFU-GM) for testing in a validated CFU-GM assay. Details are given for performing a screening test when toxicity data are not available and for passing on to an accurate inhibitory concentration-determination phase. To quantify the potential hematotoxicity of xenobiotics from their direct adverse effects on CFU-GM, the unit describes how to manage the results by means of an algorithm able to predict the acute xenobiotic exposure levels that cause maximum tolerated decreases (MTD) in absolute neutrophil count (ANC). A protocol describes a miniaturized application of the procedure in 96-well plates for high-throughput screening of compounds or for testing compounds that are available in very small quantities.

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Prevalidation of a model for predicting acute neutropenia by colony forming unit granulocyte/macrophage (CFU-GM) assay

Cited by 107 publications

References 13 publications

The selective poly(ADP-ribose) polymerase-1(2) inhibitor, CEP-8983, increases the sensitivity of chemoresistant tumor cells to temozolomide and irinotecan but does not potentiate myelotoxicity

The selective poly(ADP-ribose) polymerase-1(2) inhibitor, CEP-8983, increases the sensitivity of chemoresistant tumor cells to temozolomide and irinotecan but does not potentiate myelotoxicity

In vitromyelotoxic effects of cypermethrin and mancozeb on human hematopoietic progenitor cells

CFU‐GM Assay for Evaluation of Drug Myelotoxic Activity

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