Involvement of dual‐strand of the miR‐144 duplex and their targets in the pathogenesis of lung squamous cell carcinoma

The prognosis of patients with advanced‐stage lung squamous cell carcinoma (LUSQ) is poor, and effective treatment protocols are limited. Our continuous analyses of antitumor microRNAs (miRNAs) and their oncogenic targets have revealed novel oncogenic pathways in LUSQ. Analyses of our original miRNA expression signatures indicated that both strands of miR‐144 (miR‐144‐5p, the passenger strand; miR‐144‐3p, the guide strand) showed decreased expression in cancer tissues. Additionally, low expression of miR‐144‐5p significantly predicted a poor prognosis in patients with LUSQ by The Cancer Genome Atlas database analyses (overall survival, P = 0.026; disease‐free survival, P = 0.023). Functional assays revealed that ectopic expression of miR‐144‐5p and miR‐144‐3p significantly blocked the malignant abilities of LUSQ cells, eg, cancer cell proliferation, migration, and invasion. In LUSQ cells, 13 and 15 genes were identified as possible oncogenic targets that might be regulated by miR‐144‐5p and miR‐144‐3p, respectively. Among these targets, we identified 3 genes (SLC44A5, MARCKS, and NCS1) that might be regulated by both strands of miR‐144. Interestingly, high expression of NCS1 predicted a significantly poorer prognosis in patients with LUSQ (overall survival, P = 0.013; disease‐free survival, P = 0.048). By multivariate analysis, NCS1 expression was found to be an independent prognostic factor for patients with LUSQ patients. Overexpression of NCS1 was detected in LUSQ clinical specimens, and its aberrant expression enhanced malignant transformation of LUSQ cells. Our approach, involving identification of antitumor miRNAs and their targets, will contribute to improving our understanding of the molecular pathogenesis of LUSQ.     

Effect of vitreomacular separation on macular thickness determined by spectral-domain optical coherence tomography

Purpose

To determine the effects of vitreomacular separation on macular thickness.

Methods

This was a retrospective, observational, cross-sectional study. Average foveal and central minimum thicknesses were measured by spectral-domain optical coherence tomography (SD-OCT) in 308 eyes of 308 healthy subjects (healthy group) and 298 normal fellow eyes of 298 patients with a unilateral macular hole (MH group). Multiple regression analyses were performed to determine the effects of various factors on the macular thickness.

Results

The mean age of the healthy group was 67.3 ± 9.6 years (range 40–88 years) and that of the MH group was 67.8 ± 7.0 years (range 43–91). SD-OCT images showed that 149 eyes (48.4 %) in the healthy group and 174 eyes (58.4 %) in the MH group had a vitreomacular separation. In the healthy group, the central minimum thickness of eyes with a vitreomacular separation (196 µm) was significantly thinner than those without a vitreomacular separation (205 µm; P < 0.001). In the MH group, the average foveal thickness (234 µm) and the central minimum thickness (177 µm) in eyes with a vitreomacular separation were thinner than those without it (247 and 199 µm, respectively; both P < 0.001). Multiple regression analyses showed that a vitreomacular separation was significantly correlated with thinner central minimum thicknesses in both groups (P < 0.001) and also with the average foveal thickness in the MH group (P < 0.001).

Conclusions

A vitreomacular separation caused thinning of the central fovea in both the healthy eyes and the normal fellow eyes of unilateral MH patients; the extent of foveal thinning is greater in the MH group.

     

Long root of deciduous anterior teeth

A 24-year-old female Japanese patient presented with remarkably long roots of retained deciduous anterior teeth and permanent anterior teeth in the upper and lower jaw. Four lower anterior teeth were extracted for esthetic reasons. The patient had no apparent clinical syndrome related to the teeth or jaw, nor did there appear to be a family history of this condition. The extracted teeth and their lengths were as follows: the lower right deciduous lateral incisor was 25.55 mm long (root length, 18.95 mm); the lower left deciduous lateral incisor was 22.10 mm long (root length, 17.25 mm); the lower right deciduous canine was 27.95 mm long (root length, 20.60 mm); and the lower left deciduous canine was 23.90 mm long (root length, 17.65 mm).     

Small low-density lipoprotein and small low-density lipoprotein/total low-density lipoprotein are closely associated with intima-media thickness of the carotid artery in Type 2 diabetic patients

BACKGROUND: The intima-media thickness (IMT) of the carotid artery, as determined by ultrasonography, is useful for reflecting the extent of subclinical atherosclerosis. We investigated the relationship between IMT and the serum concentrations of small low-density lipoprotein (LDL) in diabetic patients. METHODS: The study was conducted with 27 Type 2 diabetic patients (14 males and 13 females; mean age=62.6+/-8.3 years) and 12 age-matched healthy controls. The LDL subfraction was measured using a polyacrylamide gel electrophoresis method. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) concentrations were measured by an enzyme immunoassay. The IMT was expressed as the maximum IMT (Max-IMT) and average IMT (Ave-IMT) of the carotid artery, measured by ultrasonography. RESULTS: Both the IMT and the small LDL concentrations were significantly increased in the diabetic patients compared with the healthy participants. The IMTs were significantly correlated with small LDL concentration and small LDL/total LDL more than LDL concentrations by multivariate analysis. The IMTs were not significantly correlated with the serum VEGF or PDGF concentrations. The patients with a larger IMT had a significantly higher prevalence of hypertension or ischemic heart disease than did the patients with a normal IMT. CONCLUSIONS: The increased small LDL concentrations and small LDL/total LDL, in addition to total LDL concentrations, in Type 2 diabetic patients are closely associated with increased IMT of the carotid artery.     

Serum angiotensin converting enzyme level in bronchial asthma.

Using hippuryl-L-histidyl-L-leucine as a substrate analogue, serum angiotensin converting enzyme (ACE) was spectrophotometrically estimated in patients with bronchial asthma. The mean level of asthmatic patients was significantly lower than that of the control subjects. The reduced serum ACE activities did not change during an acute asthmatic attack. Significantly lower levels of serum ACE occurred in patients with chronic asthma than in those who only suffered with occasional asthma. Serum ACE activity was not reduced when the patients were taking steroids. Serum ACE activity could not be correlated with either the systolic blood pressure or the diastolic blood pressure of our asthmatic patients. However, serum ACE activity was correlated with the serum beta-globulin fraction in asthmatic patients.     

Cerebral blood flow,oxygen and glucose metabolism with PET in progressive supranuclear palsy

Cerebral blood flow, cerebral oxygen metabolic rate and cerebral glucose metabolic rate were measured with positron emission tomography (PET) in four patients with progressive supranuclear palsy (PSP). Decreased blood flow and hypometabolism of oxygen and glucose were found in both subcortical and cortical regions, particularly in the striatum including the head of the caudate nucleus and the frontal cortex. The coupling between blood flow and metabolism was preserved even in the regions which showed decreased blood flow and hypometabolism. These findings indicated the hypofunction, as revealed by decreased blood flow and hypometabolism on PET, both in the striatum and the frontal cortex, and which may underlie the pathophysiological mechanism of motor and mental disturbance in PSP.     

Bronchial responses to enalapril in asthmatic, hypertensive patients.

The subjects, six asthmatic patients with mild essential hypertension, were aged 48 to 63 years and each was being treated with theophylline. Five patients received 10 mg of enalapril daily for two weeks and one received 5 mg for four weeks. Their bronchial responses to inhaled methacholine were measured with a modification of the 3-Hz oscillation method before and after the enalapril treatment. The patients' mean blood pressures decreased significantly from 180.7/100.3 to 152.0/93.3 mmHg after treatment. No treatment-associated changes in the frequency of coughing, the number of asthmatic attacks, or use of antiasthmatic drugs were noted. The results of the bronchial provocation tests revealed no changes in bronchial sensitivity or reactivity during treatment. Serum substance P levels were 61.3 pg/ml before treatment and 60.2 pg/ml after treatment. It is concluded that therapeutic doses of enalapril did not exacerbate asthmatic attacks or increase bronchial hypersensitivity in these asthmatic, hypertensive patients.