Metastasis is common in lung cancer and is associated with poor clinical outcomes and increased mortality. Curcumin is a natural anti-cancer agent that inhibits the metastasis of various cancers by modulating the expression of micro (mi) RNAs such as miR-98, which acts as a tumor suppressor. This study investigated the effect of curcumin on miR-98 expression and in vitro cell line growth and invasiveness in lung cancer. Curcumin treatment enhanced the expression of miR-98 and reduced that of the miR-98 target gene LIN28A as well as matrix metalloproteinase (MMP) 2 and MMP9 in vitro and in vivo. MiR-98 overexpression suppressed lung cancer cell migration and invasion by inhibiting LIN28A-induced MMP2 and MMP9 expression. Meanwhile, LIN28A level was downregulated by overexpression of miR-98 mimic. Induction of miR-98 by curcumin treatment suppressed MMP2 and MMP9 by targeting LIN28A. These findings provide insight into the mechanisms by which curcumin suppresses lung cancer cell line growth in vitro and in vivo and invasiveness in vitro.
The mRNA expression of nucleophosmin/B23 in gastric cancers (T) and the matched adjacent "normal" gastric mucosa (N) obtained from patients without any preoperative treatment were determined. Telomerase activity was detected in tumor tissues from six of seven patients. Analysis of the adjacent "normal" gastric mucosa in the same patients revealed all seven were negative for telomerase activity. In comparing clinical data for all seven patients, the stages of cancer seemed to be associated with T/N nucleophosmin/B23 mRNA expression. Cancers of later stages seemed to have higher T/N nucleophosmin/B23 mRNA ratio. After 3-4 days of 1 mM indomethacin treatment about 60-85% of gastric cultured KATO III cancer cells exhibited the features with highly condensed nuclei and decrease in cell size. Concomitant with the increase in the percentage of KATO III cells exhibiting the morphological features of apoptosis, there was a decrease in the viability of cells as determined by exclusion of trypan blue. A decline in telomerase activity in indomethacin-treated versus untreated cells was observed over times (2-4 days). The steady-state level of nucleophosmin/B23 mRNA, as determined by the levels of radioactivity of the hybridizing bands also decreased during the indomethacin treatment. At some times after the removal of indomethacin, cell growth and telomerase activity resumed in little extent (approx. 60%). When nucleophosmin/B23 antisense oligonucleotide was included in the cell culture upon removal of indomethacin, virtually no recovery of cell growth and telomerase activity were observed.
Since the clinical benefit of lung recruitment maneuvers (LRMs) is still conflicting, we performed this prospective, randomized, controlled study to investigate whether LRMs should be used in the routine management of acute respiratory distress syndrome (ARDS). This trial was conducted in four intensive care units (ICUs) to compare application of a modified stepwise LRMs with solely lung-protective ventilation in patients with moderate to severe ARDS within 72 h from the onset. The primary outcome was 28-day mortality, and the secondary outcomes were ventilator-free days and ICU-free days. We collected data on 120 ARDS patients from 2009 to 2012, and there was no difference in 28-day mortality between the two groups (28.3% vs. 30.0%, p = 0.84). However, among survivors, patients in the LRM group had a significant longer median duration of ventilator-free days (18 vs. 13 days; p = 0.04) and ICU-free days (16 vs. 11 days; p = 0.03) at 28 days than in the control group. The respiratory system compliance was significantly higher in the LRM group from day 1 to day 7. The occurrence rate of barotrauma was similar in both groups. We concluded that LRMs combined with lung-protective ventilation in early ARDS may improve patient outcomes.
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