MicroRNAs (miRNAs) are small non-protein-coding RNAs that function as endogenous negative gene regulators. Dysfunctions of miRNAs are frequently found in malignancies, including lung cancer. In this review, we summarise the current understanding of miRNAs in lung cancer tumourigenesis, and highlight their potential in overcoming drug resistance, abetting histological sub-classification techniques, and serving as biomarkers for lung cancer risk stratification and outcome prediction.

The clinical and pathological features of 22 patients, 11 males and 11 females 17-70 years of age (48.0 +/- 16.0 years), with hepatic tuberculosis were reviewed. Five patients had no evidence of extrahepatic tuberculosis (local form), and 17 had the miliary form. The clinical features of the miliary and local forms were similar with pyrexia, abdominal pain, hepatomegaly and body weight loss as the main manifestations. The biochemical findings were also quite similar in reversed albumin and globulin (A/G) ratio (2.9/3.5 vs. 3.2/3.4 g/dl) and disproportionate elevation of alkaline phosphatase (ALP) in comparison with bilirubin values but lower levels of alanine aminotransferase (ALT) (40.4 +/- 51.0 vs. 170.8 +/- 209.4 U/l; p < 0.05) and ALP (208.5 +/- 138.9 vs. 389.5 +/- 271.1 U/l; p < 0.05) in the miliary form. Patients with the local form had higher albumin (3.2 +/- 0.8 vs. 2.9 +/- 0.7 g/dl), aspartate aminotransferase (AST) (160.4 +/- 221.7 vs. 65.9 +/- 69.7 U/l), and gamma glutamyl-transpeptidase (gamma GT) (217.0 +/- 144.0 vs. 136.0 +/- 92.1 U/l), although the differences were not significant. The histopathological features of the miliary form were also similar to the local form with granuloma, caseation, acid-fast bacilli, fatty change and portal fibrosis as the main findings. The local form revealed more severe signs of hepatocytic damage while the miliary form was more wasting. The results suggest that the miliary and local forms of hepatic tuberculosis had quite similar clinical presentations and pathological features. The biochemical tests suggesting hepatic tuberculosis were reversed A/G ratio and disproportionate elevation of ALP.

In an attempt to determine which physical and biological properties could best be correlated with neurotoxic potential, seven analogs of 1-(2,4,5-trihydroxyphenyl)-2-aminoethane (1), better known as 6-hydroxydopamine, were synthesized and compared to 1 in a variety of ways both in vivo and in vitro. The analogs, in combination with the standard 1, include all eight of the 2,4,5-trisubstituted-phenyl derivatives of phenethylamine and alpha-methylphenethylamine in which the substitution is of the trihydroxy or aminodihydroxy form. Low (60 nmol) and high (300 nmol) intracerebroventricular doses of all analogs produced long-term (7 day) reduction of mouse whole brain norepinephrine (NE) and lesser depletions of dopamine (DA), and effects on serotonin were varied. The analog 1-(5-amino-2,4-dihydroxyphenyl)-2-aminopropane (8) was both more complete and more selective than the standard 1 in depleting NE. Using a histofluorometric glyoxylic acid method and Fink-Heimer silver degeneration stain, it was determined that overt neural degeneration was produced by 8. In vitro, the ease of oxidation of the eight analogs was found to be represented by a formal potential range of -130 to -212 mV vs SCE. However, there was no obvious relationship between ease of oxidation and the extent of monoamine depletion from mouse brain. Using kinetic analysis of synaptosomal accumulation of [3H]NE and [3H]DA, it was found that the standard 1 is more potent in its interaction with the DA uptake site (Ki = 12 +/- 0 microM) than the NE uptake site (Ki = 51 +/- 1 microM). A correlation analysis was used to determine that differences in NE and DA depletion by each analog could not be explained by differences in potency for in vitro uptake blockade. However, there was a correlation between the Ki for [3H]NE uptake blockade and the EC50 for synaptosomal release of preloaded [3H]NE for the eight analogs (R2 = 0.96; for log:log plot, R2 = 0.54), indicating that the results for these two in vitro tests both reflect interaction with the same NE neuronal membrane transport site. A similar correlation between Ki and EC50 was shown for all eight analogs using [3H]DA (R2 = 0.92; for log:log plot, R2 = 0.52), indicating interaction with the same DA neuronal membrane transport site. These findings demonstrate that there is no single property that can account for selectivity of action and/or potency of catecholamine neurotoxins related to 6-hydroxydopamine.

duced hepatitis is often diagnosed by exclusion, so that the To evaluate the incidence, severity, and course of ketopossibility of hepatitis C virus (HCV) infection has not been conazole-associated hepatic injury, 211 patients with excluded in most reports, because serological markers for onychomycosis were randomized by a ratio of 2:1 to re-HCV were not available before 1989. 27 Therefore, we have ceive either ketoconazole (137 patients) or griseofulvin conducted this controlled, cohort study to examine the inci-(74 patients). All of them were seronegative for hepatitis dence, severity, and clinical course of ketoconazole-induced B surface antigen (HBsAg) and anti-hepatitis C virus hepatic injury. believed and that transient subclinical injury is muchFollow-up. After the start of ketoconazole or griseofulvin therapy, more common than overt hepatitis. Therapy with ketotests for serum AST and ALT were scheduled in all patients once conazole may be continued with caution in the absence every 2 weeks for the first 3 months, and at monthly intervals thereof symptoms and/or hyperbilirubinemia, but should be after during the course of therapy. After a serum AST or ALT elevadiscontinued if overt hepatitis occurs. (HEPATOLOGY tion was detected, patients were monitored closely with clinical 1997;25:103-107.) evaluation and weekly serum AST, ALT, alkaline phosphatase, gglutamyl transpeptidase, and bilirubin measurements until normalization. It was determined before the study that ketoconazole or Ketoconazole, an imidazole derivative, has been used griseofulvin was to be discontinued promptly if clinical symptoms of widely in the treatment of systemic fungal infections.1 Sevhepatitis or hyperbilirubinemia develeped. Complete blood cell leveral case reports of mild to severe hepatic injury, including els, its differential counts, and serological markers of hepatitis A icteric and fatal cases, have been published 2-26 with an esti-virus, B virus, delta virus, and HCV, as well as anti-nuclear antibody mated incidence of symptomatic hepatic injury of 1:15,000 to and anti-smooth muscle antibody titers, were also studied when ap-1:2,000. 15,16,18 In addition, the transient asymptomatic in-propriate. Liver biopsy was routinely advised when abnormal AST crease of serum transaminase has also been reported in some or ALT levels were detected, but was performed in only one patient patients 2,3,14,[20][21][22] HDV (anti-HD) were assayed using commercial radioimmunoassays North Chicago, IL). Anti-HCV was assayed using a second-genera- Received February 5, 1996; accepted August 16, 1996. tion enzyme immunoassay