Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma

Prostaglandins play a critical role in tumor development and growth by regulating numerous biologic processes, including tumor angiogenesis, with clear prognostic and therapeutic implications. The aim of this study was to investigate the prognostic relevance of cyclooxygenase-2 (COX-2) pathway activation in head and neck squamous cell carcinoma (HNSCC). COX-2 activity was analyzed in 52 consecutive patients by assessing protein expression and prostaglandin E(2) (PgE(2)) levels and was then correlated to vascular endothelial growth factor (VEGF) expression and tumor angiogenesis. We evaluated the prognostic impact of these parameters by Kaplan-Meier and Cox survival analysis. COX-2 expression by tumor cells was closely correlated to VEGF expression and to tumor vascularization. According to Kaplan-Meier analysis, patients with COX-2 tumor overexpression and with higher PgE(2) tumor levels had significantly shorter overall survival estimates (P = 0.022 and P = 0.033, respectively). Analogously, patients with more-vascularized tumors had worse survival than those with less-vascularized cancers (P = 0.032). Cox multivariate analysis demonstrated that the most significant prognostic factors were presence of lymph node metastasis, tumor vascularization, COX-2 protein expression, and PgE(2) tumor levels. This study demonstrates a close correlation between COX-2 pathway, VEGF expression, and tumor angiogenesis in HNSCC. In addition, COX-2 overexpression and higher tumor vascularization appear to predict a shorter survival in patients with head and neck cancer.     

Positive association between circulating free insulin-like growth factor-1 levels and coronary flow reserve in arterial systemic hypertension

BACKGROUND: The reduction of coronary flow reserve (CFR) found in arterial hypertension may be due to changes in afterload, left ventricular (LV) structure, and metabolic factors. Also, insulin-like growth factor-1 (IGF-1) may be associated with the magnitude of CFR in relation to its modulating action on cardiac and endothelial function. METHODS: A total of 44 newly diagnosed, untreated hypertensive patients, who were free of diabetes mellitus and coronary artery disease, underwent M-mode analysis, second-harmonic Doppler echocardiographic assessment of CFR (dipyridamole infusion 0.56 mg/kg intravenously in four patients), determination of circulating free IGF-1, and insulin resistance. Based on CFR levels, hypertensive subjects were divided into two groups: 18 with normal CFR (> or = 2) and 26 with impaired CFR (<2). RESULTS: Patients with normal CFR had lower diastolic blood pressure, heart rate, and LV mass index but higher free circulating IGF-I than patients with reduced CFR (P < .001). Insulin resistance was not significantly different between the two groups. In a first multilinear regression analysis that included demographic and echocardiographic variables, insulin resistance was independently associated with CFR (standardized beta coefficient = -0.31, P < .05) in the overall population. However, in a subsequent model which included also IGF-1, the relationship between insulin resistance and CFR disappeared, whereas IGF-1 was the main independent determinant of CFR (beta = 0.51, P < .0002). CONCLUSIONS: Free IGF-1 circulating levels are independently associated with CFR in hypertensive individuals free of overt coronary artery disease. A possible beneficial effect exerted by IGF-1 on coronary blood flow may be supposed in arterial hypertension.     

New 1,2,3-triazolo[1,5-a]quinoxalines: synthesis and binding to benzodiazepine and adenosine receptors. II

On pursuing research about 1,2,3-triazolo[1,5-a]quinoxalines, in this paper we report synthesis and binding assays toward the benzodiazepine and A(1) and A(2A) adenosine receptors, of a new series of derivatives, bearing some structural changes (introduction of fluorine and trifluoromethyl in the seventh position, amino substituents in the fourth position, benzyl group in the fifth position and aroyl substituents in the third position). The biological tests have shown that only the 7-fluorosubstituted compounds 3a and 4a and the N-benzyl derivative 7 have a good affinity toward the benzodiazepine receptors, while only the 7-trifluoromethyl substituted compound 3b presents a moderate affinity with low selectivity toward the A(1) adenosine receptors. The other structural modifications strongly decreased biological activity.     

Biotechnological engineering of heparin/heparan sulphate: a novel area of multi-target drug discovery

Heparin is a sulphated glycosaminoglycan currently used as an anticoagulant and antithrombotic drug. It consists largely of 2-O-sulphated IdoA not l&r arrow N, 6-O-disulphated GlcN disaccharide units. Other disaccharides containing unsulphated IdoA or GlcA and N-sulphated or N-acetylated GlcN are also present as minor components. This heterogeneity is more pronounced in heparan sulphate (HS), where the low-sulphated disaccharides are the most abundant. Heparin/HS bind to a variety of biologically active polypeptides, including enzymes, growth factors and cytokines, and viral proteins. This capacity can be exploited to design multi-target heparin/HS-derived drugs for pharmacological interventions in a variety of pathologic conditions besides coagulation and thrombosis, including neoplasia and viral infection. The capsular K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor N-acetyl heparosan. The possibility of producing K5 polysaccharide derivatives by chemical and enzymatic modifications, thus generating heparin/HS-like compounds, has been demonstrated. These K5 polysaccharide derivatives are endowed with different biological properties, including anticoagulant/antithrombotic, antineoplastic, and anti-AIDS activities. Here, the literature data are discussed and the possible therapeutic implications for this novel class of multi-target "biotechnological heparin/HS" molecules are outlined.     

Second Biopsy of Axillary Sentinel Lymph Node for Reappearing Breast Cancer After Previous Sentinel Lymph Node Biopsy

Background Sentinel lymph node biopsy (SLNB) is a safe and accurate axillary staging procedure for patients with primary operable breast cancer. An increasing proportion of these patients undergo breast-conserving surgery, and 5% to 15% will develop local relapses that necessitate reoperation. Although a previous SLNB is often considered a contraindication for a subsequent SLNB, few data support this concern. Methods Between January 2000 and June 2004, 79 patients who were previously treated at our institution with breast-conserving surgery and who had a negative SLNB for early breast cancer developed, during follow-up, local recurrence that was amenable to reoperation. Eighteen of these patients were offered a second SLNB because of a clinically negative axillary status an average of 26.1 months after the primary event. Results In all 18 patients (7 with ductal carcinoma-in-situ and 11 with invasive recurrences), preoperative lymphoscintigraphy showed an axillary sentinel lymph node, with a preoperative identification rate of 100%, and 1 or more SLNs (an average of 1.3 per patient) were surgically removed. Sentinel lymph node metastases were detected in two patients with invasive recurrence, and a complete axillary dissection followed. At a median follow up of 12.7 months, no axillary recurrences have occurred in patients who did not undergo axillary dissection. Conclusions Second SLNB after previous SLNB is technically feasible and likely effective in selected breast cancer patients. A larger population and longer follow-up are necessary to confirm these preliminary data.     

Monitoring of chemical elements and oxidative damage in patients affected by Alzheimer's disease

The haematic concentration of 26 metals and the oxidative damage in 60 patients (20 males and 40 females) affected by Alzheimer's disease and 44 healthy individuals (33 males and 11 females) were compared. In patients, the following significant (p < or = 0.05) discrepancies were found: i) increment of Ca, Cd, Hg, Mg, Si and Sn, and decrement of Al, Co, Fe and Zn in serum; ii) higher concentrations of Cu, Li, Mn, Sn and Zr and lower of Fe, Hg, Mo in blood; iii) overproduction of oxidant species (SOS) and decrease of the anti-oxidant capacity (SAC) (p < or = 0.001, for both). Variables that, joined, better discriminated between patients and controls resulted to be Si, SOS, SAC, Co, Ca, Al in serum (94% of cases correctly classified) and Cu, Zr, Mo and Fe in blood (90% of cases properly categorized).     

The network of the Italian laboratories: a proficiency test on the quantification of trace elements in serum

A proficiency test on the quantification of Al, Cu, Mn, Se and Zn in serum was carried out to verify the performance of about 30 regional laboratories of the network of Italian laboratories. The exercise consisted of four runs in which the laboratories were free in choosing analytical methods to determine trace elements in freeze-dried animal serum. Laboratories performances were evaluated by the study of statistical functions as Coefficients of Variation (CV), Youden plot and Z-score value. As for Al, the results were generally characterized by good accuracy and precision, in spite of the low levels of the element (5-7 microg l(-1)). Copper determination had some problems only at low concentration (about 160 microg l(-1)--first run), in which an elevated number of anomalous data were found. Better data were achieved for Zn, for which anomalous values were mainly stragglers than outliers. Due to the low number of data for Mn (concentrations from 0.6 to 60 microg l(-1)) and Se (concentration from 45 to 106 microg l(-1)), a restricted statistical treatment was applied; for these elements high CV values were found (range from 30 to 80%). The results of this trial confirmed that participation in a proficiency test represents a benefit for all analytical laboratories. In fact, with few exceptions, most of the participants improved their performances in terms of Z-score values.     

Plaque-removing effect of a toothbrush, dental floss, and a toothpick

The ability of three different oral hygiene devices to remove 2-day-old bacterial deposits was evaluated on 21 young adults with healthy periodontia. On buccal tooth surfaces, the cleaning effect of a multitufted nylon brush was superior to that of a wooden toothpick or unwaxed dental floss. On lingual surfaces, the toothpick was as effective as the brush. On the visible portions of proximal surfaces, all three devices were equally efficient. A combined cleaning exercise with all three instruments together yielded significantly better results than did the use of each single device. Eight subjects were able to remove all disclosable deposits.