Gemcitabine inhibits the micrometastasis of non-small cell lung cancer by targeting the EpCAM-positive circulating tumor cells via the HGF/cMET pathway.

Recurrence and metastasis are responsible for the death of non-small cell lung cancer (NSCLC) patients. Circulating tumor cells (CTCs) in the metastatic pathway have proven to be essential. This pilot study evaluated the sensitivity of gemcitabine in micrometastasis and CTCs from NSCLC patients. EpCAM-positive CTCs were detected in forty patients with NSCLC at treatment initiation and disease evaluation time-points. EpCAM-positive CTCs were defined as EpCAM-positive and CD45-negative. Total RNA was isolated from EpCAM-enriched CTCs and cytokeratin levels were detected by PCR. The HGF/cMET pathway was evaluated in CTCs from patients with different treatments and in A549 cells. The EMT-related markers were analyzed by IHC. We further explored the predictive value of baseline CTCs in patients that were receiving different treatments. The median number of CTCs in NSCLC patients was 65 CTCs/ml more than in the healthy 23?fold (median, 5.2 CTCs/ml). The mean change in cell count was significantly different for patients with gemcitabine compared to patients with non-gemcitabine treatments (-86.28 vs. -15.23/ml; P<0.05). A significant decrease was noted in the expression of cytokeratin in the CTCs of the two groups (P<0.05). The HGF/cMET pathway was inactivated in CTCs and A549 cells treated with gemcitabine, and the cell migration and invasion abilities were inhibited by gemcitabine via the HGF/cMET pathway. Furthermore, the decreased cell migration and invasion abilities may also be involved in the inhibition of the epithelial-mesenchymal transition (EMT) by gemcitabine. At a median follow-up of 36 months, the CTC count was confirmed to be a robust prognostic marker in the NSCLC population (CTCs >151, median: 15.0 months and CTCs <151, median: 32.0 months). Additionally, the survival rate in the gemcitabine group (24 months) was better than in non-gemcitabine group (21 months), suggesting a therapeutic benefit for NSCLC patient survival with the common therapy plus gemcitabine. Gemcitabine treatment decreased EpCAM-positive CTCs in NSCLC patients and inhibited EMT by the HGF/cMET pathway.

Antiproliferative Activity of the Chinese Medicinal Compound, Delisheng, Compared With Rg3 and Gemcitabine in HepG2 Cells.

Delisheng consists of radix ginseng, radix astragali, venenum bufonis and mylabris. It has been reported that delisheng inhibits the proliferation of adenocarcinoma cells and stimulates their apoptosis. Delisheng can also enhance the body's immunity and induce the redifferentiation of carcinoma cells. Delisheng inhibited the proliferation of HepG2 cells in MTT assay and promoted apoptosis more effectively in contrast to the active components of ginseng extract, Rg3 and gemcitabine. It is possible that Rg3 has an important role in delisheng because they all could regulate the cell cycle, apoptosis and expression of endostatin and VEGFR-2. Delisheng caused the cell cycle to arrest at the S phase, while gemcitabine blocked the cells at the G0/G1 phase in cell cycle analysis. Consequently, the apoptosis rate of the HepG2 cell line can be increased significantly by delisheng in combination with gemcitabine, compared with the single drug. The expression of the procaspase proteins, caspase protein, and dr5 detected by Western blot were increased while bcl-2 and survivin decreased in the delisheng group, compared with controls. The observations suggest that the delisheng induced apoptotic effect might be closely related to the mitochondrial apoptosis pathway, and the death receptor signaling pathway.

Characterization of InAlAs/InGaAs/InP mid-infrared quantum cascade lasers.

A mid-infrared laser characterization system, including a GPIB programmable I-P and I-V set-up based on direct waveform measurement with extraordinary wide pulse duration and duty cycle tuning range, in conjunction with a Fourier transform infrared spectroscopy system adapted with double modulation technique, has been developed. Based on this characterization system, the characteristics of gas source MBE grown InAlAs/InGaAs/InP quantum cascade lasers (QCL), especially their thermal property, have been evaluated. The results show that in the combination of I-P, I-V and spectral measurements at various driving pulse parameters, the thermal resistance, lasing conditions as well as spectral characteristics of the mid-infrared QCL could be deduced. This characterization system is also a useful tool for the evaluation of other types of diode lasers in the mid-infrared band.