Clinical relevance of cyclin D1 protein overexpression in laryngeal squamous cell carcinoma

PURPOSE: To investigate the prognostic relevance of cyclin D1 gene overexpression in laryngeal squamous cell carcinomas (LSCCs). PATIENTS AND METHODS: The overexpression of cyclin D1 was analyzed in 149 LSCC patients with a median follow-up duration of 60 months using the DCS6 monoclonal antibody; only cases that overexpressed cyclin D1 in more than 5% of neoplastic cells were considered positive. RESULTS: Forty-eight cases (32.2%) were immunoreactive to the DCS6 antibody. Cyclin D1 overexpression was significantly associated with tobacco smoking and alcohol consumption, tumor extension, advanced clinical stage, and the presence of lymph node metastases. Univariate analysis showed that a shorter disease-free and overall survival were significantly associated with supraglottic site, tumor extension, advanced clinical stage, and cyclin D1 overexpression. At multivariate analysis, tumor extension and cyclin D1 overexpression were significantly associated with tumor recurrence, whereas tumor extension, supraglottic site and, at a borderline level of statistical significance, cyclin D1 overexpression, were associated with reduced overall survival. CONCLUSION: The overexpression of cyclin D1 in LSCC is associated with unfavorable clinicopathologic features and represents an independent significant predictor of laryngeal carcinoma prognosis, particularly for disease-free survival. This indicates that cyclin D1 evaluation may be a further useful element for selecting subgroups of patients who should be treated with more aggressive therapies.     

Regulation of monocyte IL-10 synthesis by endogenous IL-1 and TNF-alpha: role of the p38 and p42/44 mitogen-activated protein kinases

IL-10 is an anti-inflammatory cytokine with potent immunomodulatory effects, including inhibition of cytokine production. However, regulation of monocyte IL-10 production is poorly understood. In this report we have investigated the mechanisms of LPS-induced IL-10 production by human peripheral blood monocytes and demonstrate that IL-10 synthesis is uniquely dependent on the endogenous proinflammatory cytokines IL-1 and/or TNF-alpha. LPS signal transduction in monocytes has been shown to involve activation of the p38 and p42 mitogen-activated protein kinase (MAPK) cascades. The results in this paper indicate that inhibition of p38 MAPK potently inhibited the production of IL-10, IL-1beta, and TNF-alpha, whereas blockade of the p42/44 MAPK pathway, while partially inhibiting TNF-alpha and IL-1beta production, had no effect on monocyte secretion of IL-10. Furthermore, neither the inhibition of monocyte TNF-alpha induced by IL-10 nor the stimulation of soluble TNF receptor production was affected by inhibition of the p42/44 MAPK pathway, suggesting that this signaling event is not involved in either monocyte production of or anti-inflammatory responses to IL-10. These data raise the interesting possibility that proinflammatory TNF-alpha-mediated effects may be selectively blocked without modulating the induction or the response to IL-10, whereas the signaling events associated with the anti-inflammatory events induced by IL-10 remain to be elucidated.     

Continuous non-invasive blood pressure monitoring by brachial artery displacement method in high-risk surgical patients

Continuous non-invasive blood pressure (CNBP) measurements were compared to invasive radial artery pressure recordings in 26 patients with cardiac, vascular and/or pulmonary disease. Patients were studied during general anaesthesia (n = 6), regional anaesthesia (n = 10), or combined technique (n = 10) for abdominal or transurethral surgery. CNBP was obtained from a cuff placed around the upper arm and simultaneously compared to invasive pressure from the ipsilateral radial artery. A CNBP device (7001 Cortronic) used intermittent oscillometric measurement for calibration. Through a cuff continuously inflated to a pressure of 20 mmHg, a microprocessor-controlled electro-pneumatic acquisition system sensed displacements of the brachial artery wall. Amplified, digitally converted, filtered and transformed data were displayed as a continuous pulse pressure waveform and digital pressure values on the screen. The CNBP method functioned without disturbances before surgery in all patients. Intra-operative use of electrocautery or a spontaneous occurrence of warning on the screen repeatedly triggered oscillometric recalibration, hence CNBP measurements were discontinued in nine patients. Coefficients of correlation (r) of all invasive and CNBP pairs (n = 1111) were 0.68, 0.58 and 0.70 for systolic, diastolic, and mean blood pressures, respectively. Prediction errors (bias, mean +/- SD) were -13.6 +/- 22.5 mmHg (on average CNBP < invasive pressure) for systolic, +13.0 +/- 12.4 mmHg (CNBP > invasive pressure) for diastolic and +5.0 +/- 13.9 mmHg (CNBP > invasive pressure) for mean CNBP, as compared to radial artery pressure values. Absolute errors (precision) were 25.3 +/- 9.4 mmHg for systolic, 17.4 +/- 4.5 mmHg for diastolic, and 13.9 +/- 4.6 mmHg for mean CNBP. During anaesthesia induction (n = 672) the difference between consecutive measurements (trend of pressure changes) with invasive and CNBP method exceeded 20 mmHg in 90 (13.3%) instances for systolic, in 33 (4.9%) instances for diastolic, and in 45 (6.6%) instances for mean blood pressure. In conclusion, the CNBP method by brachial artery wall displacement failed to measure the blood pressure reliably and to display the trend of pressure changes correctly during anaesthesia induction. In its present form this CNBP method should not replace invasive blood pressure monitoring in high-risk patients neither for anaesthesia induction nor during non-thoracic surgical procedures.     

Sequence analysis of the CCG polymorphic region adjacent to the CAG triplet repeat of the HD gene in normal and HD chromosomes

The CAG expansion responsible for Huntington's disease (HD) is followed by an adjacent polymorphic CCG repeat region which may interfere with a PCR based diagnosis. We have sequenced this region in 52 unrelated HD patients, from both normal and HD chromosomes. Fifty percent of the normal alleles were (CCG)7(CCT)2, 48% (CCG)10(CCT)2, and 2% (CCG)7(CCT)3. In contrast (CCG)7(CCT)2 was found in 85% of the HD alleles which represents significant linkage disequilibrium with the HD mutation.