Nadia Carboni

Prone position delays the progression of ventilator-induced lung injury in rats : Does lung strain distribution play a role?

Objective:To investigate if prone position delays the progression of experimental ventilator-induced lung injury, possibly due to a more homogeneous distribution of strain within lung parenchyma. Design:Prospective, randomized, controlled trial. Setting:Animal laboratory of a university hospital. Subjects:Thirty-five Sprague Dawley male rats (weight 257 ± 45 g). Interventions:Mechanical ventilation in either supine or prone position and computed tomography scan analysis. Measurements:Animals were ventilated in supine (n = 15) or prone (n = 15) position until a similar ventilator-induced lung injury was reached. To do so, experiments were interrupted when respiratory system elastance was 150% of baseline. Ventilator-induced lung injury was assessed as lung wet-to-dry ratio and histology. Time to reach lung injury was considered as a main outcome measure. In five additional animals, computed tomography scans (GE Light Speed QX/I, thickness 1.25 mm, interval 0.6 mm, 100 MA, 100 Kv) were randomly taken at end-expiration and end-inspiration in both positions, and quantitative analysis was performed. Data are shown as mean ± sd. Measurements and Main Results:Similar ventilator-induced lung injury was reached (respiratory system elastance, wet-to-dry ratio, and histology). The time taken to achieve the target ventilator-induced lung injury was longer with prone position (73 ± 37 mins vs. 112 ± 42, supine vs. prone, p = .011). Computed tomography scan analysis performed before lung injury revealed that at end-expiration, the lung was wider in prone position (p = .004) and somewhat shorter (p = .09), despite similar lung volumes (p = .455). Lung density along the vertical axis increased significantly only in supine position (p = .002). Lung strain was greater in supine as opposed to prone position (width strain, 7.8 ± 1.8% vs. 5.6 ± 0.9, supine vs. prone, p = .029). Conclusions:Prone position delays the progression of ventilator-induced lung injury. Computed tomography scan analysis suggests that a more homogeneous distribution of strain may be implicated in the protective role of prone position against ventilator-induced lung injury.

Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients

Summary. We evaluated microvessel density (MVD) in bone marrow biopsies (BM) from multiple myeloma (MM) patients after staining with anti‐CD34 and anti‐CD105 antibodies (mAbs). The anti‐CD105 mAb was significantly more sensitive than the anti‐CD34 mAb in visualizing blood vessels both in controls and MM samples. MVD was significantly higher in MM than in controls with both anti‐CD34 and anti‐CD105 mAbs. Patients with low CD34+ MVD survived longer than patients with higher MVD (P = 0·01), whereas there was no difference in survival between patients with low and high CD105+ MVD. Multivariate analysis confirmed the independent significant association between CD34+ MVD and survival (P = 0·001).

Immunohistochemical analysis of cyclin D1 shows deregulated expression in multiple myeloma with the t(11;14)

The t(11;14)(q13;q32) chromosomal translocation, the hallmark of mantle cell lymphoma (MCL), is recurrently found in multiple myelomas (MM) by means of conventional cytogenetics. Unlike MCL, recent molecular studies of MM-derived cell lines with t(11;14) have indicated that the breakpoints are highly dispersed over the 11q13 region; however, the fact that cyclin D1 is generally overexpressed in these cell lines suggests that this gene is the target of the translocation. To evaluate further the involvement of cyclin D1 in MM, we used immunohistochemistry and fluorescence in situ hybridization to investigate cyclin D1 expression and the presence of chromosome 11 abnormalities in a representative panel of 48 MM patients (40 at diagnosis and 8 at relapse). Cyclin D1 overexpression occurred in 12/48 (25%) of cases; combined immunohistochemistry and fluorescence in situ hybridization analyses in 39 patients showed cyclin D1 positivity in all of the cases (7/7) bearing the t(11;14), in two of the 13 cases with trisomy 11, and in one of the 19 cases with no apparent abnormalities of chromosome 11. Our data indicate that the t(11;14) translocation in MM leads to cyclin D1 overexpression and that immunohistochemical analysis may represent a reliable means of identifying this lesion in MM.

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.

Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer.

PURPOSE To investigate the prognostic relevance of p21 and p27 protein expression in laryngeal squamous cell carcinoma (LSCC). PATIENTS AND METHODS We have analyzed by immunohistochemistry p21 and p27 expression in a series of 132 patients who underwent surgical resection of their LSCC and who had previously been investigated for p53 gene mutations and cyclin D1 expression. The tumors were considered low expressors when they had </= 10% of p21 and </= 50% of p27 immunoreactive neoplastic cells. RESULTS In 41 cases (31.1%), p21 was expressed in </= 10% of neoplastic cells; in 91 cases (68.9%), it was expressed in more than 10% of neoplastic cells. In 11 cases (8.3%), p27 was expressed in less than 5% of neoplastic cells; in 39 cases (29.6%), it was expressed in 5% to 50% of neoplastic cells; and in 82 cases (62.1%), it was expressed in more than 50% of the neoplastic cells. Low levels of p21 expression were associated with poor histologic differentiation and lymph node metastases. Low levels of p27 expression were associated with tumor extension and advanced clinical stage. Expression of p21 and p27 was not correlated with p53 gene status, and low p27 expression was more frequently detected in the cyclin D1-positive cases, with a borderline level of statistical significance. At univariate analysis, anatomic site, tumor extension, clinical stage, high cyclin D1 expression, and low p27 expression were significantly associated with reduced disease-free and overall survival rates. At multivariate analysis, high cyclin D1 expression and low p27 expression were the only significant covariates. The patients with a cyclin D1(+)/p27(-) phenotype had the poorest disease-free and overall survival rates. CONCLUSION Our study provides evidence that the immunohistochemical evaluation of p27 expression is a significant independent predictor of prognosis in laryngeal carcinoma.

Molecular and immunohistochemical analysis of the bcl-1/cyclin D1 gene in laryngeal squamous cell carcinomas: Correlation of protein expression with lymph node metastases and advanced clinical stage

The molecular pathogenesis of laryngeal squamous cell carcinomas (LSCCs) is still only partially understood, although genetic alterations affecting various protooncogenes or tumor suppressor genes have often been detected.

Cyclin D1 expression is predictive of occult metastases in head and neck cancer patients with clinically negative cervical lymph nodes

The aim of this study was to investigate the value of p53 and cyclin D1 gene expression in predicting the risk of occult lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC).

Clinical relevance of p53 and bcl‐2 protein over‐expression in laryngeal squamous‐cell carcinoma

We investigated immunohistochemically the clinical relevance of the over‐expression of the apoptosis‐regulating proteins p53 and bcl‐2 in a homogeneous series of 149 laryngeal squamous‐cell carcinomas. p53 was over‐expressed in 75 cases and bcl‐2 in 39 cases. p53 and bcl‐2 co‐expression was found in 21 cases. p53 and bcl‐2 immunoreactivity was significantly associated with poor histological differentiation and lymph‐node metastases. Moreover, a significant statistical correlation was found between bcl‐2 expression, supraglottic tumor site and advanced disease stage. p53/bcl‐2 co‐expression was significantly associated with poor differentiation, tumor extension, the presence of lymph‐node metastases and advanced clinical stage. Univariate analysis showed that a lower probability of survival was significantly associated with supraglottic site, tumor extension, advanced clinical stage and p53/bcl‐2 co‐expression, but not with p53 or bcl‐2 considered separately. In multivariate analysis, only tumor extension and supraglottic site retained their prognostic value. Our data suggest that clinical staging remains the most reliable predictive indicator of survival in patients with laryngeal carcinoma. Int. J. Cancer (Pred. Oncol.) 79:263–268, 1998.© 1998 Wiley‐Liss, Inc.

Chromogranin A and B and secretogranin II in prostatic adenocarcinomas: Neuroendocrine expression in patients untreated and treated with androgen deprivation therapy

Neuroendocrine (NE) expression in prostatic adenocarcinomas (PACs) has been related to an adverse clinical course, but the reported data are not unequivocal.

The predictive value of p53, MDM-2, cyclin D1 and Ki67 in the progression from low-grade dysplasia towards carcinoma of the larynx

To evaluate the predictive role of the oncogenes p53, MDM-2 and cyclin D1, and the proliferative marker Ki67, in the progression from low-grade dysplasia to carcinoma of the larynx. We studied immunohistochemically a series of 32 low-grade pre-neoplastic laryngeal lesions, 10 of which progressed to invasive carcinoma. Immunoreactivity in more than 10 per cent of the dysplastic cells was detected in five cases immunostained with anti-p53 (approximately 15 per cent), in two with anti-MDM-2 (approximately six per cent), and 11 with anti-Ki67 antibodies (approximately 34 per cent), whereas none of the cases showed cyclin D1 overexpression. No significant association was found between p53 and MDM-2 immunoreactivity and the evolution to carcinoma; on the contrary, Ki67 expression was detectable in all but one of the 10 cases developing an infiltrative tumour (90 per cent), and in two of the 22 cases that did not progress (approximately nine per cent) (p = 0.01). These findings indicate that immunohistochemical assessment of the proliferative index in bioptic samples of dysplastic laryngeal mucosa may be useful in selecting patients who should undergo a more specific follow-up evaluation.