Clinical efficacy and safety of anti-PD-1/PD-L1 treatments in non-small cell lung cancer (NSCLC).

Aims: The present study was performed to investigate the efficacy and safety of anti-programmed death-1 (PD-1)/programmed death-ligand-1 (PD-L1) treatments in non-small cell lung cancer (NSCLC).Methods: The potential articles were searched from Pubmed and Embase. The end points included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events. p < .05 or I2 ≥ 50% meant obvious heterogeneity, and the random-effects model was adopted for pooled analysis, otherwise, the fixed-effects model was used. Subgroup analysis was performed based on the treatment line. Potential publication bias was tested with Begg's funnel plot.Results: Eight eligible articles were included. OS rate of NSCLC patients was prolonged by anti-PD-1/PD-L1 treatments (HR = 0.685, 95%CI = 0.632-0.742), as well as PFS (HR = 0.821, 95%CI = 0.721-0.936). Meanwhile, anti-PD-1/PD-L1 treatments could greatly enhance the ORR (RR = 1.646, 95%CI = 1.382-1.961), with fewer adverse events (RR = 0.800, 95%CI = 0.688-0.931). Subgroup analysis indicated that anti-PD-1/PD-L1 treatments as second-line treatment could significantly improve the survival of patients without adverse events. The overall results were robust, without significant publication bias (p = .532).Conclusion: Anti-PD-1/PD-L1 treatments show better clinical efficacy and higher safety than chemotherapy in NSCLC.

Detection of hybridization of single-strand DNA PCR products in temperature change process by a novel metal-clamping piezoelectric sensor.

Oligonucleotide probes on the sensor surface can be hybridized with single-strand DNA (ssDNA) that is formed from PCR products in ice bath after degeneration. Thus, detection of PCR products by piezoelectric sensors requires the participation of ssDNA PCR products in ice bath. When PCR products in ice bath are added into the buffer of the sensor well at room temperature, there will be a temperature change process during mixing. However, it still remains unclear whether the temperature change affects the frequency baseline stability of the sensor and the result judgment, which is the basic condition for detecting hybridization of nucleic acid. In this study, we detected the hybridization of HPV PCR products during temperature change process by a self-designed adjustable metal-clamping piezoelectric sensor. The study mainly involves sensor adjustment, probe immobilization and ice bath sample addition (at different concentrations and different volumes). The response curve of basic frequency in temperature change process showed three stages, i.e., increase, decrease to baseline, and continuous decrease to stability. The early increase of frequency and duration of the time can reach 55+/-7.4 Hz and 39 min when 40 microL sample (0-1 degrees C) was added into 110 microL buffer (25 degrees C). The frequency increase effect caused by temperature difference at early stage depends on the volume ratio of two liquids and on the temperature difference. The results indicate that we should pay more attention to possibly small volume of PCR products in ice bath and minor temperature difference of two liquids in operation.

The effect of focal adhesion kinase gene silencing on 5-fluorouracil chemosensitivity involves an Akt/NF-kappaB signaling pathway in colorectal carcinomas.

Multicellular resistance (MCR) is produced because multicellular spheroids (MCSs) are formed with a broad cell-cell connection when cultured in three-dimensions, which limits the clinical treatment efficacy in solid tumors. Focal adhesion kinase (FAK) plays an important role in apoptosis, survival and cell adhesion between cells and their extracellular matrix. In this study, we investigated the expressions of FAK, Akt and NF-kappaB in human colorectal cancer (CRC), and the effects of FAK gene silencing on MCSs formation and 5-fluorouracil (5-FU) chemosensitivity in colon carcinoma MCSs culture cells. In CRC samples, FAK, Akt and NF-kappaB were overexpressed. The positive expression of FAK correlated notably with lymph node metastasis and cellular differentiation. Positive expressions of Akt and NF-kappaB were significantly related to cellular differentiation and lymph node metastasis, respectively. Furthermore, positive expression of FAK correlated with that of Akt and NF-kappaB. The expression of FAK was inhibited significantly by a small hairpin RNA targeting FAK. Knockdown of FAK reversed the formation and aggregation of MCSs, significantly decreased the 50% inhibitory concentration of 5-FU, and markedly increased MCS culture cells apoptosis. These effects were associated with reduced levels of Akt and NF-kappaB. These results indicate that suppressing FAK expression potentiated 5-FU-induced cytotoxicity and contributed to its chemosensitizing effect by suppressing Akt/NF-kappaB signaling in colon carcinoma MCS culture cells. These data also imply that FAK mediates MCR of CRC through the survival signaling pathway FAK/Akt/NF-kappaB.

Knockdown of focal adhesion kinase reverses colon carcinoma multicellular resistance.

Chemotherapy resistance in solid tumors is broad and encompasses diverse unrelated drugs. Three-dimensional multicellular spheroids (MCSs) are a good model for studying in vitro drug resistance. In the current study, we investigated the role of focal adhesion kinase (FAK) in 5-fluorouracil (5-FU) chemoresistance in colon carcinoma MCS culture cells. The expression of FAK was inhibited significantly by specific small hairpin RNA targeting FAK. The suppression of FAK expression did not affect the growth of spheroid cells. However, silencing of FAK combined with 5-FU treatment significantly decreased the 50% inhibitory concentration (IC(50)) of 5-FU and markedly increased the population of apoptosis cells, which was associated with the reduction of the levels of Akt and nuclear factor-kappa B (NF-kappaB). Moreover, knockdown of FAK could inhibit tumor growth and increase the sensitivity of the tumor to 5-FU in the nude mouse xenograft. These results indicate that while not affecting cellular proliferation in the absence of 5-FU, RNA interference targeting FAK potentiated 5-FU-induced cytotoxicity in vitro and in vivo, and partially reversed multicellular resistance, which may contribute to its chemosensitizing effect through efficiently suppressing Akt/NF-kappaB activity.

[Efficacy of combined gemcitabine and cisplatin in the treatment of advanced non-small cell lung cancer].

BACKGROUND: No chemotherapeutic regimen and agent are effective for most patients with advanced non-small cell lung cancer (NSCLC). This study is designed to evaluate the efficacy and toxicity of the combination of gemcitabine and cisplatin in the treatment of NSCLC.. METHODS: Sixty cases of NSCLC in stage III and IV were treated with gemcitabine 1200mg/m² by intravenous infusion on 1st and 8th days, and cisplatin 100mg/m² by intravenous infusion on 1st day or 30mg/m² by intravenous infusion on 1st and 8th days in a 28-day cycle. Each patient was treated at least for 2 cycles. RESULTS: An objective response was obtained in 46.67% of patients (3 complete and 25 partial responses), whereas 22 patients had no change and 10 patients were progressive. The response rate was 57.14% in patients without prior chemotherapy and 22.22% in patients with prior treatment. Significant difference existed between the two groups (P < 0.05). The main toxicities were leukopenia and thrombocytopenia, but didn't influence the chemotherapy. CONCLUSIONS: The combination of gemcitabine and cisplatin is a feasible, well-tolerated and effective scheme in the treatment of advanced NSCLC.