MicroRNA160 Modulates Plant Development and Heat Shock Protein Gene Expression to Mediate Heat Tolerance in Arabidopsis.

Global warming is causing a negative impact on plant growth and adversely impacts on crop yield. MicroRNAs (miRNAs) are critical in regulating the expression of genes involved in plant development as well as defense responses. The effects of miRNAs on heat-stressed Arabidopsis warrants further investigation. Heat stress increased the expression of miR160 and its precursors but considerably reduced that of its targets, ARF10, ARF16, and ARF17. To study the roles of miR160 during heat stress, transgenic Arabidopsis plants overexpressing miR160 precursor a (160OE) and artificial miR160 (MIM160), which mimics an inhibitor of miR160, were created. T-DNA insertion mutants of miR160 targets were also used to examine their tolerances to heat stress. Results presented that overexpressing miR160 improved seed germination and seedling survival under heat stress. The lengths of hypocotyl elongation and rachis were also longer in 160OE than the wild-type (WT) plants under heat stress. Interestingly, MIM160 plants showed worse adaption to heat. In addition, arf10, arf16, and arf17 mutants presented similar phenotypes to 160OE under heat stress to advance abilities of thermotolerance. Moreover, transcriptome and qRT-PCR analyses revealed that HSP17.6A, HSP17.6II, HSP21, and HSP70B expression levels were regulated by heat in 160OE, MIM160, arf10, arf16, and arf17 plants. Hence, miR160 altered the expression of the heat shock proteins and plant development to allow plants to survive heat stress.

Gefitinib-induced intestinal obstruction in advanced non-small cell lung carcinoma: A case report.

Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor, which is used to treat patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations. Dermatological reactions are the most common adverse events associated with gefitinib treatment; other adverse effects, including diarrhea, nausea, stomatitis and an asymptomatic elevation of liver enzymes have also been reported. The present study describes a patient with intestinal obstruction who was successfully undergoing treatment with gefitinib for primary and metastatic neoplasms. Gefitinib-induced intestinal obstruction has not been previously reported; therefore, careful monitoring of gastrointestinal symptoms should be conducted throughout the course of gefitinib-treated malignancies.

Recrudescent meibomian gland carcinoma treated with Xeloda: case report.

PURPOSE: To observe the curative effect of Xeloda in meibomian gland carcinoma. METHODS: We treated a 53-year-old woman, who had recrudescent meibomian gland carcinoma, with Xeloda. RESULTS: The mass was much smaller with decreased amount of overflow pus after 4 cycles of chemotherapy with Xeloda. CONCLUSIONS: Xeloda played a significant role in treating recrudescent meibomian gland carcinoma in this patient.

Effects of PI3K inhibitor NVP-BKM120 on acquired resistance to gefitinib of human lung adenocarcinoma H1975 cells.

The effects of class I PI3K inhibitor NVP-BKM120 on cell proliferation, cell cycle distribution, cellular apoptosis, phosphorylation of several proteins of the PI3K/AKT signaling pathway and the mRNA expression levels of HIF1-α, VEGF and MMP9 in the acquired gefitinib resistant cell line H1975 were investigated, and whether NVP-BKM120 can overcome the acquired resistance caused by the EGFR T790M mutation and the underlying mechanism were explored. MTT assay was performed to detect the effect of gefitinib, NVP-BKM120, NVP-BKM120 plus 1 µmol/L gefitinib on growth of H1975 cells. The distribution of cell cycle and apoptosis rate of H1975 cells were examined by using flow cytometry. The mRNA expression levels of tumor-related genes such as HIF1-α, VEGF and MMP9 were detected by using real-time quantitative PCR. Western blotting was used to detect the expression level of phosphorylated proteins in the PI3K/AKT signaling pathway, such as Ser473-p-AKT, Ser235/236-p-S6 and Thr70-p-4E-BP1, as well as total AKT, S6 and 4E-BP1. The results showed that the NVP-BKM120 could inhibit the growth of H1975 cells in a concentration-dependent manner, and H1975 cells were more sensitive to NVP-BKM120 than gefitinib (IC50:1.385 vs. 15.09 µmol/L respectively), whereas combination of NVP-BKM120 and gefitinib (1 µmol/L) did not show more obvious effect than NVP-BKM120 used alone on inhibition of cell growth (P>0.05). NVP-BKM120 (1 µmol/L) increased the proportion of H1975 cells in G0-G1 phase and the effect was concentration-dependent, and 2 µmol/L NVP-BKM120 promoted apoptosis of H1975 cells. There was no significant difference in the proportion of H1975 cells in G0-G1 phase and apoptosis rate between NVP-BKM120-treated alone group and NVP-BKM120 plus genfitinib (1 µmol/L)-treated group or between DMSO-treated control group and gefitinib (1 µmol/L)-treated alone group (P>0.05 for all). It was also found that the mRNA expression levels of these genes were down-regulated by NVP-BKM120 (1 µmol/L), and NVP-BKM120 (1 µmol/L) or NVP-BKM120 (1 µmol/L) plus gefitinib (1 µmol/L) obviously inhibited the activation of Akt, S6 and 4E-BP1 as compared with control group, but single use of gefitinib (1 µmol/L) exerted no significant effect. These data suggested that NVP-BKM120 can overcome gefitinib resistance in H1975 cells, and the combination of NVP-BKM120 and gefitinib did not have additive or synergistic effects. It was also concluded that NVP-BKM120 could overcome the acquired resistance to gefitinib by down-regulating the phosphorylated protein in PI3K/AKT signal pathways in H1975 cells, but it could not enhance the sensitivity of H1975 cells to gefitinib.