Tumor antigens and antigen-presenting capacity in breast cancer.

AIMS: Cancer cells frequently express antigens capable of being recognized by the host immune system; however, any resultant immune response is often ineffective. This may be related in part to tumor-induced defects in antigen presentation. We screened for dendritic cell infiltration, tumor MHC II expression and associated lymphocytic reaction in the context of three established breast tumor antigens. METHODS: Forty primary breast tumors were evaluated by immunohistochemical techniques for expression of her2/neu, p53, and MUC1 and MHC class II molecules. Twenty-five samples were further analyzed for p53 mutations by PCR-SSCP analysis and DNA sequencing. The phenotype of tumor-infiltrating inflammatory cells was evaluated using the following markers: CD1a, MHC Class II, CD3, CD45, and CD45RO. RESULTS: Tumors with p53 mutations and overexpression, but not her2/neu or MUC1 overexpressing tumors, more frequently harbored marked CD1a+ dendritic cell infiltrates. An overall correlation between CD1a+ cell infiltrates and HLA class II expression on tumor cells (p = 0.0008) was also observed and these tumors had greater CD45RO+ lymphocytic infiltrates. CONCLUSIONS: In breast cancer, p53 mutations may present a more visible signal to the immune system and hence provide a better target for immunotherapy. Infiltrating CD1a positive cells are associated with a more dense tumor lymphocytic infiltrate and tumor cell expression of MHC II molecules.     

Concomitant boost radiation and concurrent cisplatin for advanced head and neck carcinomas. Preliminary results of a phase II, single-institutional trial

INTRODUCTION: This study aims to asses the effectiveness and toxicity of boost radiotherapy concomitant and concurrent cisplatin for patients with locally advanced head and neck cancer (LAHNC). MATERIAL AND METHODS: There were 30 patients included in a prospective, phase II single-institution trial and of whom, 29 were at AJCC stage IV and 1 at stage III. Treatment consisted of radiotherapy acceleration fractionation with concomitant boost, 72 Gy, and 2 cycles of concomitant cisplatin (20 mg/m2/day continuous infusion; days 1-5 and 29-33). Amifostine, (i.v. 200 mg/m2) was administered to 26 prior to the first fraction of radiotherapy. Endpoints of the study were quality-of-life (QL), overall survival, and local control of disease. RESULTS: Complete response (CR) was achieved in 23 patients (77%), 2 patients had partial response (PR) (7%), 4 had no response (13%), and 1 was not evaluated for response. The 2-year overall survival and loco-regional control were 60% and 56%, respectively. Main toxicity was grade 3 or 4 mucositis in 93% of the patients. QL scores (questionnaire QLQC30; version 3.0) and the HN cancer module QLQ-HN35) showed a worsening in areas related to the treatment e.g. dry mouth, problems stretching the mouth, and sticky saliva. CONCLUSIONS: this combination modality is active, but toxic, in the treatment for LAHNC. Concomitant boost radiotherapy is probably, not the best radiotherapy schema for combining with chemotherapy in LAHNC.     

Mechanical and physical properties of silorane and methacrylate-based composites

ObjectivesThis study measured the degree of conversion (DC), sorption, solubility and microhardness of methacrylate (Filtek Z250 and Filtek Z350XT) and silorane-based composites (Filtek P90).MethodsDC was measured using near infrared spectroscopy immediately and 24 h after the photoactivation. Sorption and solubility measurements were performed after 24 h, 4 weeks and 12 weeks of storage in water. Knoop microhardness was measured after 24 h and after thermal cycling. The data were statistically analyzed using ANOVA followed by Tukey's, Tamhane or paired t-tests (α = 0.05).ResultsThe DC for P90 (37.22 ± 1.46) was significantly lower than the Z250 (71.44 ± 1.66) and Z350 (71.76 ± 2.84). Water sorption was highest in the Z250 and lowest in the P90. All the tested composites exhibited similar values after 24 h of immersion, and no significant differences were observed. No significant differences were observed between the solubilities of the P90 composite (12 weeks) and the Z250 or Z350 composites (4 weeks). KHN values were less elevated for the P90 composite and similar for the Z250 and Z350 composites. An effect of thermal cycling on KHN values was observed for all the composites (p < 0.001).ConclusionsSilorane produced the lowest DC and KHN values and exhibited lower water sorption and solubility compared to methacrylate-based composites. These differences suggest that silorane composites exhibit better hydrolytic stability after 3 months of water immersion compared to conventional methacrylate-based composites.Clinical significanceSilorane had higher hydrolytic stability after 3 months of water immersion than the methacrylate-based resins, despite the lower values of DC and KHN recorded.     

Decremental atriofascicular accessory pathway with bidirectional conduction: delineation of atrial and ventricular insertion by radiofrequency current application

A 17-year-old girl with a corrected complex congenital heart disease and recurrent episodes of supraventricular tachycardia was referred for catheter ablation. Electrophysiologic studies revealed the presence of an accessory pathway (AP) with bidirectional conduction and decremental properties. We demonstrated a course parallel to the node-His AV conduction system. Transient abolition of the bidirectional conduction through the AP was obtained by radiofrequency application to the ventricular insertion located in the distal right bundle branch and to the atrial insertion, located in the mid-anterior atrial septum. Radiofrequency application at the low anterior atrial septum, above the His bundle, successfully abolished AP conduction without affecting AV nodal conduction. Demonstration of the course and insertions of the AP, its bidirectional decremental conduction properties, and the association with a complex congenital heart disease are exceptional and interesting findings and raise the possibility of an accessory AV node with a parallel conduction pathway to the right bundle branch.     

Improved malignancy prediction by B3 breast lesions subclassification

Core-needle biopsy (CNB) of breast lesions can be classified into 5 categories according to lesion type and associated risk of malignancy. B3 category (lesion of uncertain malignant potential) constitutes a challenging problem in clinical decision, with most ending in excisional biopsy. Therefore, the aim of this study was to establish the incidence of malignancy on excision biopsy of B3 lesions and assess if subclassification (in B3a and B3b categories) according to the presence of atypia in otherwise B3 lesions better predicts malignancy on excision. Forty-eight cases with diagnosis of B3 lesion on CNB and matched surgical excision specimen were included to evaluate the positive predictive value (PPV) and odds for malignancy in CNB. All cases were further subclassified into B3a and B3b categories. B3 category lesions had an overall PPV for malignancy of 12.5% and significant low odds of malignancy of 0.14. When subclassified, B3b (lesions with atypia) demonstrated a higher PPV for malignancy (36.36%) with a nonsignificant odds. Inversely, B3a (lesions without atypia) demonstrated a PPV for malignancy of only 5.41% and a significant low odds of malignancy of only 0.06. The described low rate of malignancy in some of B3 lesions additionally reinforces the practice of avoiding surgical excision in selected patients and provides data that additionally support B3 lesion subclassification according to the presence of atypia. Subclassification of B3 category can further refine the current classification of associated risk of malignancy with possible implications in clinical management.     

Comparison of High Ribavirin Induction Versus Standard Ribavirin Dosing, Plus Peginterferon-α for the Treatment of Chronic Hepatitis C in HIV-Infected Patients: The PERICO Trial

Background.?Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. Methods.?HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180?μg/d) plus either RBV standard dosing (1000 or 1200?mg/d if <75 or ≥75?kg, respectively) or RBV induction (2000?mg/d) along with subcutaneous erythropoietin β (450?IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. Results.?A total of 357 patients received ≥1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14?μg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3?mg/dL; P?相似文献