Integrin α11 in non–small cell lung cancer is associated with tumor progression and postoperative recurrence

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11β1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non–small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT‐PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence‐free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.     

Effect of calcitonin on total body bone mineral contents of experimental osteoporotic rats determined by dual photon absorptiometry

Summary Total body bone mineral (TBBM) content in rats was measured by dual photon absorptiometry (DPA). TBBM showed significant increases over 4 weeks in control groups with significant bone loss over the same time in prednisolone-injected rats on low calcium feed. Daily injections of calcitonin significantly reduced loss of bone mass. Both prednisolone- and prednisolone-calcitonin-injected groups showed significantly elevated serum alkaline phosphatase with the prednisolone-calcitonin group also exhibiting elevated serum calcium and phosphate levels, confirming the impact of the experimental protocol. TBBM measured by DPA in all groups correlated well (r=0.928,P<0.001 n=20) with the total ash weight suggesting that the method reflects total skeletal mineral content in the small animal. TBBM measurement by DPA proves well-suited to monitoring bone mineral in a small animal experimental setting.     

Usefulness of magnetic motor evoked potentials in the surgical treatment of hemiplegic patients with intractable epilepsy.

Five hemiplegic patients with intractable epilepsy were studied with transcranial magnetic stimulation (TMS) before and after various surgical treatments. These patients had unilateral widespread cerebral lesions acquired at various times, including congenital, infantile and childhood injury. Motor evoked potentials (MEPs) of the abductor pollicis brevis (APB) muscles were simultaneously recorded on both sides following TMS of the motor cortex in the respective hemisphere using a figure-8 or circular coil. In all patients with congenital disease, the abolition of motor function in the affected hemisphere was estimated by magnetic MEPs, and the hemiplegia did not deteriorate after functional hemispherectomy (HS) was performed in two of them. In two patients with acquired disease, HS was not performed because it was shown by magnetic maps that the motor function in the affected hemisphere remained. Furthermore, it was shown by electric MEPs using subdural electrodes that a patient who had had encephalitis in early childhood had a reorganised motor area in the parietal cortex of the affected hemisphere. The present findings indicate that magnetic MEPs are a very useful non-invasive method of assessing whether the motor area in the affected hemisphere can be resected in hemiplegic patients with intractable epilepsy.     

A new experimental trial using repeated heating every 24 hours for local hyperthermic therapy with bleomycinin vivo

This report presents the effect of repeated heating every 24 hrs using bleomycin (BLM) which, although seemingly contrary to the usual agreement that hyperthermia should be carried out with a long interval due to thermotolerance, holds many possibilities. FM3A cells on the foot pad of C3H mouse were immersed in a heated water bath at 43 and 44°C for 30 min. The effect of repeated heating was appreciated by an improved growth curve and 50 day survival compared to mice which received heating twice with a 96-hr interval. Repeated heating every 24 hrs 5 times with BLM suppressed tumor growth significantly as compared to heating twice with a 96-hr interval without BLM. The longest survival time was obtained by the repeated heating with BLM among all protocols. There is therefore a good possibility that more effective results could be obtained clinically by repeated heating over a short period.     

Activation of the Akt/GSK3beta signaling pathway mediates survival of vulnerable hippocampal neurons after transient global cerebral ischemia in rats.

Recent studies have revealed that the phosphatidylinositol 3-kinase (PI3-K) pathway is involved in apoptotic cell death after experimental cerebral ischemia. The serine-threonine kinase, Akt, functions in the PI3-K pathway and prevents apoptosis by phosphorylation at Ser473 after a variety of cell death stimuli. After phosphorylation, activated Akt inactivates other apoptogenic factors, including glycogen synthase kinase-3beta (GSK3beta), thereby inhibiting cell death. However, the role of Akt/GSK3beta signaling in the delayed death of hippocampal neurons in the CA1 subregion after transient global cerebral ischemia (tGCI) has not been clarified. Transient global cerebral ischemia for 5 mins was induced by bilateral common carotid artery occlusion combined with hypotension. Western blot analysis showed a significant increase in phospho-Akt (Ser473) and phospho-GSK3beta (Ser9) in the hippocampal CA1 subregion after tGCI. Immunohistochemistry showed that expression of phospho-Akt (Ser473) and phospho-GSK3beta (Ser9) was markedly increased in the vulnerable CA1 subregion, but not in the ischemic-tolerant CA3 subregion. Double staining with phospho-GSK3beta (Ser9) and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed different cellular distributions in the CA1 subregion 3 days after tGCI. Phosphorylation of Akt and GSK3beta was prevented by LY294002, a PI3-K inhibitor, which facilitated subsequent DNA fragmentation 3 days after tGCI. Moreover, transgenic rats that overexpress copper/zinc-superoxide dismutase, which is known to be neuroprotective against delayed hippocampal CA1 injury after tGCI, had enhanced and persistent phosphorylation of both Akt and GSK3beta after tGCI. These findings suggest that activation of the Akt/GSK3beta signaling pathway may mediate survival of vulnerable hippocampal CA1 neurons after tGCI.     

RETRACTED ARTICLE: Effects of dobutamine on the fatigued diaphragm: A comparison with dopamine

We examined the effects of dopamine (DOA) 10 μg·kg⁻¹·min⁻¹ I.V. and dobutamine (DOB) 10 μg·kg⁻¹. min⁻¹ I.V. on the contractility of the fatigued diaphragm in 26 anesthetized, mechanically ventilated dogs. Animals were divided into two groups of 13 each: the DOA and DOB groups. Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Diaphragmatic contractility was assessed from changes in transdiaphragmatic pressure (P_di). After diaphragmatic fatigue, P_di at low-frequency (20 Hz) stimulation decreased significantly compared with the prefatigue value (P<0.05), whereas no change in P_di was observed at high-frequency (100 Hz) stimulation. In the fatigued diaphragm, P_di at both stimuli increased with an infusion of either DOA (P<0.05) or DOB (P<0.05). The increase of P_di at 20 Hz stimulation was significantly larger in the DOB group compared with that of the DOA group (P<0.05). In each group, P_di at both stimuli decreased after the cessation of administration. The integrated diaphragmatic electric activity (E_di) in the two groups did not change at any frequency of stimulation throughout the study. We conclude that DOB in comparison with DOA is more effective in improving the contractility of the fatigued diaphragm.