Objective:To investigate the effects of CD137 signaling on the regulation of CD3-CD56+NK cells function. Methods: CD3-CD56+NK cells were treated with CD137 mAb or mouse IgG1 isotype control to study the effects of CD137 signaling on the function of CD3-CD56+NK cells. Cytotoxicity was measured by LDH activity in the supernatants of cell cultures; NKG2D and LFA-1 expression on CD3-CD56+NK cells were analyzed by flow cytometry. Results: CD137 was expressed on activated CD3-CD56+NK cells. The CD137 mAb enhanced the ability of CD3-CD56+NK cells to kill lung cancer cells(A549);Further studies revealed that the expression of NKG2D and LFA-1 was significantly increased in activated cells,and blockade of NKG2D and LFA-1 dramatically attenuated CD3-CD56+NK cytolysis of A549 cancer cells. Conclusion: CD137 signaling increases the ability of CD3-CD56+NK cells to kill cancer cells via up-regulating the expression of NKG2D and LFA-1.
Objective: To examine plasma microRNA-21 (miR-21) level in patients with non-small cell lung cancer (NSCLC) and its potential correlation with chemotherapeutic response. Methods: 77 NSCLC patients and 36 age and sex-matched healthy controls were included. Plasma miR-21 concentration was examined using a quantitative real-time reverse transcription polymerase chain reaction assay (qRT-PCR). Potential correlation between plasma mir-21 concentrations with chemotherapeutic responses was analyzed in 35 patients with advanced NSCLC (stages IIIB and IV). Results: Plasma miR-21 was significantly higher in NSCLC patients relative to the healthy controls (P<0.0001). As a biomarker, plasma mir-21 had a receiver operating characteristic (ROC) curve area of 0.729 with 61.04% sensitivity and 83.33% specificity. Chemotherapeutic response in the 35 patients with advanced NSCLC (stages IIIB and IV) included partial response (PR) (n=11), stable disease and progression disease (SD+PD) (n=24). The overall response rate (CR+PR) was 31.4%. Plasma miR-21 in patients who achieved PR was significantly lower than those who did not respond (SD+PD) (P=0.0487), and comparable to that of the healthy controls (P=0.2744). Conclusion: Plasma miR-21 is a good biomarker for NSCLC, and could be used to predict responses to chemotherapy.
Juan Wei Lian-ke Liu Wen Gao Cheng-jun Zhu Yi-qian Liu Ting Cheng Yong-qian Shu
Studies have shown cell-free microRNA(miRNA) circulating in the serum and plasma with specific expression in cancer,indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy.This study was to investigate whether plasma miRNA-21(miR-21) can be used as a biomarker for the early detection of non-small cell lung cancer(NSCLC) and to explore its association with clinicopathologic features and sensitivity to platinum-based chemotherapy.We used real-time RT-PCR to investigate the expression of miR-21 in the plasma of 63 NSCLC patients and 30 healthy controls and correlated the findings with early diagnosis,pathologic parameters,and treatment.Thirty-five patients(stages IIIB and IV) were evaluable for chemotherapeutic responses:11 had partial response(PR);24 had stable and progressive disease(SD+PD).Plasma miR-21 was significantly higher in NSCLC patients than in age-and sex-matched controls(P<0.001).miR-21 was related to TNM stage(P<0.001),but not related to age,sex,smoking status,histological classification,lymph node status,and metastasis(all P>0.05).This marker yielded a receiver operating characteristic(ROC) curve area of 0.775(95% CI:0.681-0.868) with 76.2% sensitivity and 70.0% specificity.Importantly,miR-21 plasma levels in PR samples were several folds lower than that in SD plus PD samples(P=0.049),and were close to that in healthy controls(P=0.130).Plasma miR-21 can serve as a circulating tumor biomarker for the early diagnosis of NSCLC and is related to the sensitivity to platinum-base chemotherapy.
Juan Wei Wen Gao Cheng-Jun Zhu Yi-Qian Liu Zhu Mei Ting Cheng Yong-Qian Shu
