Midkine mRNA level in peripheral blood mononuclear cells is a novel biomarker for primary non-small cell lung cancer: a prospective study

2012 ◽  
Vol 139 (4) ◽  
pp. 557-562 ◽  
Author(s):  
Zhihong Ma ◽  
Hongwei Li ◽  
Bin Wang ◽  
Qibin Shen ◽  
Enhai Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prospective Study ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Mrna Level ◽  
Small Cell ◽  
Small Cell Lung ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
A Prospective Study

Phase I Study of G3139, a bcl-2 Antisense Oligonucleotide, Combined With Carboplatin and Etoposide in Patients With Small-Cell Lung Cancer

2004 ◽  
Vol 22 (6) ◽  
pp. 1110-1117 ◽  
Author(s):  
Charles M. Rudin ◽  
Mark Kozloff ◽  
Philip C. Hoffman ◽  
Martin J. Edelman ◽  
Robyn Karnauskas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Small Cell ◽  
Time To Progression ◽  
Small Cell Lung ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Extensive Stage

Purpose Bcl-2 is expressed in the majority of cases of small cell lung cancer (SCLC) and may contribute to chemotherapeutic resistance. Bcl-2 suppression by G3139 (oblimersen sodium), a phosphorothioate oligonucleotide complementary to the bcl-2 mRNA, has the potential to enhance the antitumor efficacy of standard cytotoxic chemotherapy. A dose-finding study was performed evaluating the combination of G3139, carboplatin, and etoposide in patients with previously untreated extensive stage SCLC. Patients and Methods Sixteen patients were treated in three consecutive cohorts. Cohort 1 (n = 5) received G3139 5 mg/kg/d on days 1 to 8 of a 21 day cycle, with carboplatin area under the curve (AUC) = 6 on day 6, and etoposide 80 mg/m2/d on days 6 to 8. In cohort 2 (n = 4), carboplatin dose was reduced to AUC = 5. In cohort 3 (n = 7), G3139 dose was escalated to 7 mg/kg/d. G3139 plasma concentrations and Bcl-2 protein levels in peripheral blood mononuclear cells were evaluated. Results Two of three assessable patients in cohort 1 experienced cycle 1 dose-limiting toxicity (grade 4 neutropenia). No cycle 1 dose-limited toxicity was observed in cohorts 2 or 3. Of 14 patients assessable for response, partial response was documented in 12 patients (86%), and stable disease in two. Median time to progression was 5.9 months. Carboplatin and etoposide administration did not appear to alter G3139 pharmacokinetics. No evidence of Bcl-2 suppression in peripheral blood mononuclear cells was observed. Conclusion The combination of G3139, carboplatin, and etoposide is well tolerated and results in an encouraging response rate and time to progression in patients with extensive stage SCLC.

scholarly journals Differential Kinase Activation in Peripheral Blood Mononuclear Cells from Non-Small-Cell Lung Cancer Patients Treated with Nivolumab

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 762 ◽  
Author(s):  
Gaëlle Noé ◽  
Audrey Bellesoeur ◽  
Lisa Golmard ◽  
Audrey Thomas-Schoemann ◽  
Pascaline Boudou-Rouquette ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Cluster A ◽  
Nsclc Patients

In the era of precision medicine, research of biomarkers for identification of responders to nivolumab therapy is a major challenge. Peripheral blood mononuclear cells (PBMC) could be an interesting surrogate tissue for identifying pharmacodynamic biomarkers. The aim of this exploratory study was to investigate the global serine/threonine kinase (STK) activity in PBMC from non-small-cell lung cancer (NSCLC) patients using a high throughput kinomic profiling method. PamChip® microarrays were used to explore the STK kinomic profile in PBMC from 28 NSCLC patients before nivolumab initiation (D0) and on day 14 (D14) of the first administration. Two clusters of patients (A and B) were identified at D0, median overall survival (OS) tended to be longer in cluster A than in B (402 vs. 112.5 days, respectively; p = 0.15). Interestingly, the PD-L1 tumor cell score (p = 0.045), the count of CD8+ cells (p = 0.023) and the total body weight (p = 0.038) were statistically different between the clusters. On D14, clusters C and D were identified. Greater activity of most STK, especially those of the PI3K/Akt signaling pathway, was noticed among cluster C. No significant difference between C and D was observed regarding OS. Considering the small number of patients, results from this preliminary study are not conclusive. However, the 4-fold longer median OS in cluster A paves the way to further investigate, in a larger cohort of NSCLC patients, the benefit of basal STK kinomic profile in PBMC to identify responders to nivolumab therapy.

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