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Lipopolysaccharide-Induced CXCL10 mRNA Level and Six Stimulant-mRNA Combinations in Whole Blood: Novel Biomarkers for Bortezomib Responses Obtained from a Prospective Multicenter Trial for Patients with Multiple Myeloma.

Watanabe T, Mitsuhashi M, Sagawa M, Ri M, Suzuki K, Abe M, Ohmachi K, Nakagawa Y, Nakamura S, Chosa M, Iida S, Kizaki M - PLoS ONE (2015)

Bottom Line: Six stimulant-mRNA combinations; that is, lipopolysaccharide (LPS)-granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS-CXCL chemokine 10 (CXCL10), LPS-CCL chemokine 4 (CCL4), phytohemagglutinin-CCL4, zymosan A (ZA)-GMCSF and ZA-CCL4 showed significantly higher induction in the complete and very good partial response group than in the stable and progressive disease group, as determined by both parametric (t-test) and non-parametric (unpaired Mann-Whitney test) tests.Moreover, LPS-induced CXCL10 mRNA expression was significantly suppressed 2-3 days after the first dose of bortezomib in all patients, as determined by both parametric (t-test) and non-parametric (paired Wilcoxon test) tests, whereas the complete and very good partial response group showed sustained suppression 1-3 weeks after the first dose.Thus, pretreatment LPS-CXCL10 mRNA and/or the six combinations may serve as potential biomarkers for the response to bortezomib treatment in MM patients.

View Article: PubMed Central - PubMed

Affiliation: Hematology Division, National Cancer Center Hospital, Tokyo, Japan.

ABSTRACT
To identify predictive biomarkers for clinical responses to bortezomib treatment, 0.06 mL of each whole blood without any cell separation procedures was stimulated ex vivo using five agents, and eight mRNAs were quantified. In six centers, heparinized peripheral blood was prospectively obtained from 80 previously treated or untreated, symptomatic multiple myeloma (MM) patients with measurable levels of M-proteins. The blood sample was procured prior to treatment as well as 2-3 days and 1-3 weeks after the first dose of bortezomib, which was intravenously administered biweekly or weekly, during the first cycle. Six stimulant-mRNA combinations; that is, lipopolysaccharide (LPS)-granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS-CXCL chemokine 10 (CXCL10), LPS-CCL chemokine 4 (CCL4), phytohemagglutinin-CCL4, zymosan A (ZA)-GMCSF and ZA-CCL4 showed significantly higher induction in the complete and very good partial response group than in the stable and progressive disease group, as determined by both parametric (t-test) and non-parametric (unpaired Mann-Whitney test) tests. Moreover, LPS-induced CXCL10 mRNA expression was significantly suppressed 2-3 days after the first dose of bortezomib in all patients, as determined by both parametric (t-test) and non-parametric (paired Wilcoxon test) tests, whereas the complete and very good partial response group showed sustained suppression 1-3 weeks after the first dose. Thus, pretreatment LPS-CXCL10 mRNA and/or the six combinations may serve as potential biomarkers for the response to bortezomib treatment in MM patients.

No MeSH data available.


Related in: MedlinePlus

LPS-induced CXCL10 expression before and after bortezomib treatment.Each point/line represents the fold increase in LPS-induced CXCL10 expression in each patient in the (A) CR+VGPR, (B) PR and (C) SD+PD groups. The statistically significant difference between the pretreatment (D0) and 2–3 days (D2-3) or 1–3 weeks (W1-3) after intravenous administration of the first dose of bortezomib during the first cycle groups is shown. t: Student’s t-test, W: Wilcoxon test.
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pone.0128662.g002: LPS-induced CXCL10 expression before and after bortezomib treatment.Each point/line represents the fold increase in LPS-induced CXCL10 expression in each patient in the (A) CR+VGPR, (B) PR and (C) SD+PD groups. The statistically significant difference between the pretreatment (D0) and 2–3 days (D2-3) or 1–3 weeks (W1-3) after intravenous administration of the first dose of bortezomib during the first cycle groups is shown. t: Student’s t-test, W: Wilcoxon test.

Mentions: As shown in Fig 2, LPS-induced CXCL10 mRNA expression was significantly suppressed 2–3 days after the first dose of bortezomib in all groups, as determined by both parametric (t-test) and non-parametric (paired Wilcoxon test) tests, while the CR+VGPR group showed sustained suppression even 1–3 weeks after treatment. This significant level of inhibition was only observed for LPS-induced CXCL10.


Lipopolysaccharide-Induced CXCL10 mRNA Level and Six Stimulant-mRNA Combinations in Whole Blood: Novel Biomarkers for Bortezomib Responses Obtained from a Prospective Multicenter Trial for Patients with Multiple Myeloma.

Watanabe T, Mitsuhashi M, Sagawa M, Ri M, Suzuki K, Abe M, Ohmachi K, Nakagawa Y, Nakamura S, Chosa M, Iida S, Kizaki M - PLoS ONE (2015)

LPS-induced CXCL10 expression before and after bortezomib treatment.Each point/line represents the fold increase in LPS-induced CXCL10 expression in each patient in the (A) CR+VGPR, (B) PR and (C) SD+PD groups. The statistically significant difference between the pretreatment (D0) and 2–3 days (D2-3) or 1–3 weeks (W1-3) after intravenous administration of the first dose of bortezomib during the first cycle groups is shown. t: Student’s t-test, W: Wilcoxon test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482752&req=5

pone.0128662.g002: LPS-induced CXCL10 expression before and after bortezomib treatment.Each point/line represents the fold increase in LPS-induced CXCL10 expression in each patient in the (A) CR+VGPR, (B) PR and (C) SD+PD groups. The statistically significant difference between the pretreatment (D0) and 2–3 days (D2-3) or 1–3 weeks (W1-3) after intravenous administration of the first dose of bortezomib during the first cycle groups is shown. t: Student’s t-test, W: Wilcoxon test.
Mentions: As shown in Fig 2, LPS-induced CXCL10 mRNA expression was significantly suppressed 2–3 days after the first dose of bortezomib in all groups, as determined by both parametric (t-test) and non-parametric (paired Wilcoxon test) tests, while the CR+VGPR group showed sustained suppression even 1–3 weeks after treatment. This significant level of inhibition was only observed for LPS-induced CXCL10.

Bottom Line: Six stimulant-mRNA combinations; that is, lipopolysaccharide (LPS)-granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS-CXCL chemokine 10 (CXCL10), LPS-CCL chemokine 4 (CCL4), phytohemagglutinin-CCL4, zymosan A (ZA)-GMCSF and ZA-CCL4 showed significantly higher induction in the complete and very good partial response group than in the stable and progressive disease group, as determined by both parametric (t-test) and non-parametric (unpaired Mann-Whitney test) tests.Moreover, LPS-induced CXCL10 mRNA expression was significantly suppressed 2-3 days after the first dose of bortezomib in all patients, as determined by both parametric (t-test) and non-parametric (paired Wilcoxon test) tests, whereas the complete and very good partial response group showed sustained suppression 1-3 weeks after the first dose.Thus, pretreatment LPS-CXCL10 mRNA and/or the six combinations may serve as potential biomarkers for the response to bortezomib treatment in MM patients.

View Article: PubMed Central - PubMed

Affiliation: Hematology Division, National Cancer Center Hospital, Tokyo, Japan.

ABSTRACT
To identify predictive biomarkers for clinical responses to bortezomib treatment, 0.06 mL of each whole blood without any cell separation procedures was stimulated ex vivo using five agents, and eight mRNAs were quantified. In six centers, heparinized peripheral blood was prospectively obtained from 80 previously treated or untreated, symptomatic multiple myeloma (MM) patients with measurable levels of M-proteins. The blood sample was procured prior to treatment as well as 2-3 days and 1-3 weeks after the first dose of bortezomib, which was intravenously administered biweekly or weekly, during the first cycle. Six stimulant-mRNA combinations; that is, lipopolysaccharide (LPS)-granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS-CXCL chemokine 10 (CXCL10), LPS-CCL chemokine 4 (CCL4), phytohemagglutinin-CCL4, zymosan A (ZA)-GMCSF and ZA-CCL4 showed significantly higher induction in the complete and very good partial response group than in the stable and progressive disease group, as determined by both parametric (t-test) and non-parametric (unpaired Mann-Whitney test) tests. Moreover, LPS-induced CXCL10 mRNA expression was significantly suppressed 2-3 days after the first dose of bortezomib in all patients, as determined by both parametric (t-test) and non-parametric (paired Wilcoxon test) tests, whereas the complete and very good partial response group showed sustained suppression 1-3 weeks after the first dose. Thus, pretreatment LPS-CXCL10 mRNA and/or the six combinations may serve as potential biomarkers for the response to bortezomib treatment in MM patients.

No MeSH data available.


Related in: MedlinePlus