MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small-cell lung cancer: a prospective case-control study.

BACKGROUND: Non-small-cell lung cancer (nsclc) is associated with very poor overall survival because 70% of patients present with locally advanced or metastatic disease at the time of diagnosis. Micrornas (mirnas) are a class of short, noncoding rna molecules whose presence in samples of biologic fluids such as sputum has demonstrated promise as a potential means of detecting nsclc. We investigated the stage-specific nsclc detection potential of an efficient panel of 3 mirnas (mir-21, mir-210, mir-372) using a single sputum sample. METHODS: A single spontaneously expectorated sputum sample was prospectively collected from 21 early nsclc (≤stage ii) patients, 22 advanced nsclc (≥stage iii) patients, and 10 control subjects. Mirna expression profiles were determined by quantitative real-time polymerase chain reaction and were analyzed by unsupervised hierarchical cluster analysis. RESULTS: Mean tumour size (±95% confidence interval) in the early and advanced nsclc patients was 3.3 cm ± 0.9 cm and 4.8 cm ± 0.7 cm respectively. Adenocarcinoma constituted 61.9% of the early and 45.5% of the advanced nsclc cases respectively. In comparing the early nsclc group with the control group, the mirna panel yielded a diagnostic sensitivity of 67% and a specificity of 90.0%. For the advanced nsclc group, the mirna panel detected nsclc with a sensitivity and specificity of 64% and 100% respectively. CONCLUSIONS: A sputum mir-21, mir-210, and mir-372 expression profile might provide a sensitive and highly specific means for detecting nsclc. Sputum mirna analysis demonstrates promise as a potential complementary screening tool.

Serum concentration of cystatin C is not affected by cellular proliferation in patients with proliferative haematological disorders.

BACKGROUND: Recent reports have shown elevated concentrations of serum cystatin C (CC) in patients with solid tumours. The aim of our study was to investigate whether patients with proliferative haematological disorders have increased serum concentrations of CC compared with normal subjects. METHODS: Full blood count, serum CC, beta2-microglobulin (beta2M) and serum creatinine were determined in 27 apparently healthy subjects and 35 patients with proliferative haematological disorders. Creatinine clearance was calculated using the Cockroft-Gault formula. RESULTS: CC and beta2M showed a significant correlation with each other (r=0.96, P<0.0001). Serum beta2M (P=0.001) and the serum beta2M:CC ratio (P=0.001) were significantly higher in the patients with normal renal function than in controls, but serum CC was not significantly different (P=0.08). CC did not show a significant correlation with blood count parameters. DISCUSSION: Compared with beta2M and the beta2M:CC ratio, serum CC is not influenced by cell proliferation in haematological disorders.

Effects of delta-aminolaevulinic acid upon electrical activity of rat spinal cord in vivo.

Bath applied delta-aminolaevulinic acid (ALA, 1-1000 microM), significantly depressed the frequency of spontaneous antidromic activity in the lumbar dorsal roots, and the amplitude of the monosynaptic component of the dorsal root-evoked ventral root reflex, in isolated rat spinal cord in a concentration-related manner. In contrast bath concentrations up to 1 mM ALA were found to produce no significant change in either the conducted afferent volley, nor field potentials recorded in the lumbar dorsal horn. These results indicate that the raised levels of ALA found in cerebrospinal fluid during porphyrias and lead poisoning may contribute to the neurological symptoms of these diseases.

Postnatal changes in the dorsal root reflex in the isolated spinal cord of the hamster, Mesocricetus auratus.

Spontaneous activity has been demonstrated in the lumbar dorsal roots of isolated spinal cord preparations taken from animals ranging in age from 2 to 65 days. Peaks of activity were recorded at 2 and 5 weeks of age, with mean firing frequencies of 33 Hz and 28 Hz respectively. The firing frequency in weeks 3 and 4 was lower (15 Hz) as was the frequency in cords taken from animals older than 6 weeks. The pattern of the spontaneous dorsal root activity changed during the first 5 weeks of life. In cords taken from animals less than 10 days old, the roots fired single action potentials, producing a single broad peak in Inter Spike Interval plots (ISI). Dorsal root recordings made from cords taken from animals in weeks 2 and 3 of life exhibited both single spikes and bursts of action potentials. By the end of the third week of life, individual spike activity had declined and the bursts of action potentials characteristic of the adult pattern had become dominant, producing a bimodal ISI plot. Cross correlation analysis of dorsal root and dorsal horn activity in lumbar segments up to five segments apart, revealed an increasing degree of correlation developing over the first 4 weeks of postnatal life. Dorsal horn responses to dorsal root stimulation in cords taken from young animals were prolonged, lasting in excess of 250 msec. In the third week of life, the duration of the excitatory component of the response was reduced to approximately 50 msec by the development of an inhibitory phase.

Postnatal changes in the role of NMDA in the isolated spinal cord of the hamster, Mesocricetus auratus.

The frequency of spontaneous activity recorded from lumbar dorsal roots and the lumbar dorsal horn of isolated spinal cord preparations taken from hamsters aged between 2 days to 8 weeks showed an age dependent sensitivity to 1 mM Mg2+ and 5 microM AP5. Spontaneous dorsal root and dorsal horn activity in cords from animals less than 3 weeks of age was depressed by 1 mM Mg2+ and 5 microM AP5. Cords taken from animals older than 3 weeks showed significantly less depression of spontaneous activity. The application of 10 microM NMDA to the cord produced a small (33%) depression in spontaneous dorsal root and dorsal horn activity in cords from 4 to 6 week old animals. Cords from younger animals exhibited a complex response to NMDA, with an initial increase in spontaneous activity followed by a profound (77%) depression of the firing rate. These results indicate that there are substantial changes taking place in the pharmacology of the dorsal horn during the early weeks of life, and care must be exercised when extrapolating results obtained from neonatal preparations to adult animals.