Efficacy and safety of EGFR­TKIs plus Shenqi Fuzheng injection for non-small cell lung cancer patients with EGFR-sensitive mutations.

PURPOSE: The aim of this retrospective study is to evaluate the impact on efficacy and safety between epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) alone and in combination with Shenqi Fuzheng injection (SFI) in patients with advanced NSCLC harboring epidermal growth factor receptor (EGFR) activating mutations. METHODS: Retrospectively, information of 88 patients receiving EGFR-TKIs as first-line targeted treatment or in combination with SFI in the Affiliated Drum Tower Hospital of Nanjing University Medical College and the Affiliated Cancer Hospital of Anhui University of Science and Technology was collected. The primary endpoint was to assess progression-free survival (PFS) and safety of EGFR-TKIs alone or in combination with SFI. RESULTS: Between January 2016 and December 2019, a total of 88 patients were enrolled in this research, including 50 cases in the EGFR-TKIs single agent therapy group and 38 cases in the SFI combined with EGFR-TKIs targeted-therapy group. The median PFS (mPFS) of monotherapy group was 10.50 months (95%CI 9.81-11.19), and 14.30 months (95%CI 10.22-18.38) in the combination therapy group. Compared to the single EGFR-TKIs administration, combinational regimen with SFI exhibited a lower incidence of rash and diarrhea in patients and was even better tolerated. CONCLUSIONS: SFI combined with the first-generation EGFR-TKIs are more efficient, can prominently prolong the PFS and attenuate the adverse reactions in patients with advanced NSCLC with EGFR-sensitive mutations.

PPARα agonist fenofibrate relieves acquired resistance to gefitinib in non-small cell lung cancer by promoting apoptosis via PPARα/AMPK/AKT/FoxO1 pathway.

Recent studies show that intracellular accumulation of cholesterol leads to acquired resistance to gefitinib in non-small cell lung cancer (NSCLC) cells. In this study we investigated how to regulate the cholesterol levels in gefitinib-resistant NSCLC cells. We showed that intracellular cholesterol levels in gefitinib-resistant cell lines (PC-9/GR, H1975, H1650, and A549) were significantly higher than that in gefitinib-sensitive cell line (PC-9). Treatment with gefitinib (5 µM) significantly increased intracellular cholesterol levels in PC-9/GR, H1975, and H1650 cells. Gefitinib treatment downregulated the expression of PPARα, LXRα, and ABCA1, leading to dysregulation of cholesterol efflux pathway. We found that a lipid-lowering drug fenofibrate (20, 40 µM) dose-dependently increased the expression of PPARα, LXRα, and ABCA1, decreased the intracellular cholesterol levels, and enhanced the antiproliferative effects of gefitinib in PC-9/GR, H1975, and H1650 cells. We revealed that fenofibrate increased the gefitinib-induced apoptosis via regulating the key proteins involved in the intrinsic apoptosis pathway. In PC-9/GR, H1975 and H1650 cells, fenofibrate dose-dependently increased the expression of AMPK, FoxO1, and decreased the expression of AKT, which were remarkably weakened by knockdown of PPARα. In PC-9/GR cell xenograft mice, combined administration of gefitinib (25 mg · kg-1 · d-1) and fenofibrate (100 mg · kg-1 · d-1) caused remarkable inhibition on tumor growth as compared to treatment with either drug alone. All the results suggest that fenofibrate relieves acquired resistance to gefitinib in NSCLC by promoting apoptosis via regulating PPARα/AMPK/AKT/FoxO1 pathway. We propose that combination of gefitinib and fenofibrate is a potential strategy for overcoming the gefitinib resistance in NSCLC.

[Effect and Mechanism of Attapulgite and Its Modified Materials on Bioavailability of Cadmium in Soil].

The effect of attapulgite (magnesium aluminium phyllosilicate) and its modified materials on the extractability of soil Cd and the accumulation of Cd in lettuce (Lactuca sativa) were investigated using a pot-culture experiment, and the immobilization mechanism of attapulgite and its modified materials was explored through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The results showed that attapulgite and its modified materials could significantly reduce the Cd concentration in Lactuca sativa, with maximum reductions of 41.0% and 56.5%, respectively, and attapulgite modified materials treatments appeared more efficient than attapulgite treatments in reducing Cd uptake of Lactuca sativa. The saturated adsorption capacity for the adsorption of Cd2+ on attapulgite rose distinctly after being modified. Attapulgite and its modified materials could significantly reduce Cd content in soil CaCl2 extract at the dosage of 1%, with the maximum reduction rates of 34.2% and 34.3%, respectively. The attapulgite formed a complex to immobilize Cd mainly through the surface silanol and Cd2+ complexation reaction, while the modified attapulgite formed a complex mainly through the complexation of Cd2+ with carboxyl groups which existed in addition to the complexation with surface hydroxyl, thus reducing the mobility of Cd2+ and achieving remediation of Cd-contaminated soil. In summary, attapulgite and its modified materials can both be used for remediation of Cd-contaminated soil, and the mechanisms for this function were found to be different.

[Preparation, characterization and property of bamboo-like alpha-Fe2 O3 nanobars].

Firstly, hydroxide iron precursor was prepared by the co-precipitation method through using nitric iron as the source of iron, ammonia as precipitants, and poly-glycol as dispersant. Secondly, the precursor was calcined at 450 degrees C for 2 h under the protection of nitrogen. Finally, the images and structures of resultant powders were investigated by transmission electron microscopes (TEM), X-ray diffraction (XRD), Raman spectrum and the near-edge X-ray absorption fine structure (NEXAFS), respectively, and the magnetic property of resultant powders was measured by a vibrating sample magnetometer (VSM HH-50). The experimental results of TEM show that the products are composed of Fe2 O3 nano-particles with sizes in the range of 50-100 nm and bamboo-like Fe2 O3 nanobars about 10 nm in diameter. The experimental results of XRD and spectrum illuminate that the structures of products are alpha-Fe2 O3. Moreover, magnetic properties measurement reveals that the products exhibit typical magnetic hysteresis loops of ferromagnetism materials, and their saturation magnetization and coercive force are approximately 64.65 emu x g(-1) and 15.13 Oe, respectively.