Cell-cycle-associated markers and clinical outcome in human epithelial cancers: a tissue microarray study

The development and progression of epithelial cancers are the result of an imbalance in signals promoting and inhibiting cellular proliferation and apoptosis. The aim of this study is to evaluate the expression of cell-cycle and apoptosis regulators and correlate them with clinical outcome in the most frequent carcinomas, in order to establish common prognostic biomarkers independent of cancer origin. Using tissue microarrays (TMAs), we have analysed the immuno-expression of Ki-67, Bcl-2, Bax, cyclin D1, cyclin D3, CDK1, CDK2, CDK6, p16, p21, and p27 in a series of 205 carcinomas of the large bowel, breast, lung and prostate (80, 73, 37 and 15 cases, respectively). By univariate analysis, positivity for p27, p16 and Bcl-2 was associated with better overall survival (P<0.0135, P<0.0442 and P<0.0001, respectively). The risk of mortality was 2.3-fold greater in patients without Bcl-2 expression. TMA immunohistochemical analysis identified a subset of epithelial cancers with overlapping alterations in cell-cycle checkpoints, apoptosis regulators and tumour suppressor pathways. We found that in most common epithelial cancers, regardless of origin, Bcl-2 appears to be the key biological factor influencing clinical behaviour.     

Fluorescent in situ hybridization heating pretreatment: the key is temperature control

Fluorescent in situ hybridization (FISH) is a very useful tool for diagnostic and prognostic purposes in pathology. However, many laboratories still experience troubles when applying FISH to paraffin material. To overcome these difficulties, different pretreatments which include enzymatic digestion have been described. Usually, previous to digestion, a heating step is performed. The aim of this study was to compare the efficiency of the heating step with different buffers and different heating methods. We conclude that the main factor in the heating pretreatment is the temperature control, irrespective of the buffer used. Best results are obtained with any buffer by heating the slides to 99°C for 15 min followed by 10 min at room temperature.     

Rhinocerebral mucormycosis. Presentation of two cases and review of the literature

Mucormycosis is a serious infection with a fulminating course caused by opportunistic fungi. The territory most frequently affected is the maxillofacial region. The disease develops in patients with severe metabolic and immunological disorders. We present two cases that illustrate its severity and the need for early diagnosis and aggressive treatment.     

Differential effects of amiodarone on Vmax and conduction velocity in anisotropic myocardium.

Despite its widespread clinical use, the precise mechanism of action of amiodarone (AMI) has not been completely defined. We examined the effects of AMI (20 micrograms/ml) on Vmax and on conduction velocity (theta) during longitudinal (LP) and transverse (TP) propagation with respect to fiber orientation, in 10 strips of uniform anisotropic epicardial muscle obtained from the left ventricle of adult canine hearts. Mean values +/- SEM (standard error of the mean) were calculated as normalized values (beat 50/beat 1) after 4 h of AMI superfusion at five different basic cycle lengths (BCL). Vmax decreased from 0.99 +/- 0.01 at a BCL of 5,000 ms to 0.43 +/- 0.03 at a BCL of 300 ms during LP. During TP, Vmax decreased from 0.99 +/- 0.01 at a BCL of 5,000 ms to 0.54 +/- 0.05 at a BCL of 300 ms. The differences in the relative changes between both directions at a BCL of 300 ms, as well as at intermediate values of 1,000, 500, and 400, were significant (p less than 0.01). theta during LP (theta L) was depressed from 0.99 +/- 0.01 at a BCL of 5,000 ms to 0.80 +/- 0.04 at a BCL of 300 ms. In contrast, theta during TP (theta T) did not change as the BCL was decreased. In consequence, theta L was significantly more depressed than theta T at BCLs shorter than 1,000 ms (p less than 0.05). Moreover, theta T after AMI was not statistically different from control at any BCL studied. The lack of depression of theta T associated with a marked depression of Vmax during either LP or TP suggests that in addition to its sodium channel blocking properties, AMI could produce a decrease in the effective axial resistivity.     

Effects of lidocaine on Vmax and conduction velocity in uniform anisotropic canine ventricular muscle: possible role of its binding-rate constants.

We evaluated the effect of lidocaine (5 micrograms/ml) on Vmax and conduction velocity during longitudinal and transverse propagation to fiber orientation in strips of uniform anisotropic ventricular muscle from adult canine hearts. Tissues were markedly anisotropic, with conduction velocities 3.2 times faster during longitudinal propagation than during transverse propagation to the long axis of the fibers, and with the greatest values of Vmax associated with the slowest conduction velocities. After addition of lidocaine, Vmax (normalized values with respect to control for each cycle length, expressed as mean +/- SEM) decreased from 0.99 +/- 0.02 at a cycle length of 1,000 ms to 0.86 +/- 0.02 at a cycle length of 300 ms during longitudinal propagation. During transverse propagation, Vmax decreased from 0.99 +/- 0.03 at a cycle length of 1,000 ms to 0.87 +/- 0.03 at a cycle length of 300 ms. The differences in the relative changes between both directions at these cycle lengths, as well as with intermediate values of 500, 400, and 350 ms, were not significant. Similar results were obtained for conduction velocity. We conclude from these findings that under these experimental conditions the effects of lidocaine are characterized by a relative change both in Vmax and conduction velocity that is almost the same during longitudinal and transverse propagation at all cycle lengths explored. Moreover, the rapid binding-rate constants reported for lidocaine may play a significant role in determining the characteristics of Vmax and conduction velocity depressions in both directions.