A new preclinical femoral head osteonecrosis model in sheep

Introduction  

Animal models have been used as insight into the pathogenesis of osteonecrosis, even though most have failed to reproduce all stages of human disease, limiting progression in experimental treatment modalities. A new surgically induced animal model of femoral head osteonecrosis in sheep is presented.     

A comparative study of HER2/neu amplification and overexpression using fluorescencein situ hybridization (FISH) and immunohistochemistry (IHC) in 101 breast cancer patients

The HER2/neu protooncogene is expressed in the breast, ovarian, gastric and prostatic tumors. Studies done in a number of laboratories have demostrated that 25%–30% of breast cancer contain overexpression of HER2/neu gene. A comparative analysis of the amplification and overexpression of HER2/neu using fluorescencein situ hybridization (FISH) and immunohistochemistry (IHC) was performed to determine the correlation between both techniques. In this study, FISH with HER2/neu probe (Path Vysion) is compared to immunohistochemistry (rabbit anti-human c-erbB-2-DAKO) in a series of 101 prospective human breast cancer specimens. Among 25 patients with score of IHC 3+, 23 (92%) were detected amplified by FISH and in two cases we found overexpression (3+) but without gene amplification. Out of 46 cases with 2+ by IHC, we found 43 not amplified, two moderately amplified (<10 copies) and one highly amplified (>10 copies) (6.5%). No patient with IHC O or 1+, presented amplification of HER2/neu. A good correlation between both techniques was found. FISH technique should have clinical utillity overoat in cases with 2+.     

Neoplasias malignas secundarias después de un trasplante de progenitores hematopoyéticos en edad pediátrica

Introduction

Survival after hematopoietic stem cell transplantation has improved dramatically in recent years. Unfortunately, there is an increased risk of subsequent malignant neoplasms (SMN) in this population and this represents a significant cause of late mortality.

Comparison of the Radiation Therapy Oncology Group recursive partitioning classification and Union Internationale Contre le Cancer TNM classification for patients with head and neck carcinoma

BACKGROUND: Prognostic models need to be tested in external validation studies to assess generalizability. Recursive partitioning analysis (RPA), a prognostic system based on the creation of a classification tree, has been proposed as a classification method in patients with head and neck carcinoma. The aim of this study was to compare the RPA and Union Internationale Contre le Cancer (UICC) TNM classification systems in patients with head and neck carcinoma treated consecutively in a single center. METHODS: A total of 2166 patients with carcinomas of the oral cavity, oropharynx, hypopharynx, and larynx was classified according to both the RPA and the TNM classification systems, and the results were compared. The endpoints considered were observed survival and survival free of locoregional tumor. The two methods of classification were evaluated objectively by use of measures of intrastage homogeneity (hazard consistency), interstage heterogeneity (hazard discrimination), predictive power (outcome prediction), and patient distribution between stages (balance). RESULTS: When the endpoint considered was observed survival, there were no clinically relevant differences between the two classifications. However, when the endpoint was locoregional control, the RPA system was sensitive to the type of treatment used, and it was not generalizable. CONCLUSIONS: To evaluate generalizability, new classification proposals need external validation studies that objectively measure the quality of the model. The performance of the RPA system was not reproducible in our cohort of patients when the endpoint evaluated was locoregional control.     

Choline acetyltransferase expression does not identify early pathogenic events in fetal SMA spinal cord

We investigated the expression of choline acetyltransferase, a specific marker for cholinergic neurons, in control and spinal muscular atrophy fetuses and newborns. By immunoblot we observed at 12 and 15 weeks a similar pattern of choline acetyltransferase expression in spinal muscular atrophy with respect to controls, although at 22 weeks this expression was reduced, probably due to a smaller number of motor neurons in the spinal muscular atrophy spinal cord. By immunohistochemistry, the counting of positive and negative motor neurons for choline acetyltransferase immunostaining in control and spinal muscular atrophy fetuses showed a similar proportion at all stages analyzed. The choline acetyltransferase-negative motor neurons were of similar appearance in both groups. After birth, chromatolytic motor neurons were detected in spinal muscular atrophy, all of which were choline acetyltransferase-negative. Our results in spinal muscular atrophy fetuses indicate that choline acetyltransferase immunostaining does not identify early events in neuronal pathogenesis and suggest that the spinal muscular atrophy surviving motor neurons may not be dysfunctional during this period. Furthermore, spinal muscular atrophy choline acetyltransferase-negative motor neurons showed detectable pathological changes only after birth, indicating that choline acetyltransferase is a late marker for motor neuron degeneration and not a primary contributing factor in this process.     

Challenging the neuronal MIBG uptake by pharmacological intervention: effect of a single dose of oral amitriptyline on regional cardiac MIBG uptake

Purpose Imaging with metaiodobenzylguanidine (MIBG) is used for the assessment of neuronal dysfunction in various cardiovascular disorders. Although valuable information is obtained by resting MIBG imaging, it is conceivable that competitive interference with the re-uptake mechanism would exaggerate MIBG defects and might unmask subclinical neuronal dysfunction. Tricyclic antidepressants, such as amitriptyline, have been reported to significantly increase cardiac MIBG washout and inhibit uptake into presynaptic neurons. This study was undertaken to assess whether a single oral dose of amitriptyline could influence cardiac MIBG distribution.Methods Six patients (aged 62–81 years; four males, two females) who had demonstrated a normal cardiac MIBG scan during work-up for movement disorders were studied. The patients underwent a second ¹²³I-MIBG study after oral administration of 25 mg amitriptyline within 1 week. Single-photon emission computed tomography images were acquired at 4 h to assess the regional distribution of MIBG, after generation of polar maps and employing a 20-segment model. Mean percentage of peak activity was calculated for each segment at rest and after amitriptyline administration.Results After amitriptyline administration, there was a decrease in regional MIBG uptake in 10±4 segments per patient [62/120 segments (52%): 37 segments with a 5–10% decrease, 25 segments with a >10% decrease]. This change was statistically significant in lateral (P=0.003), apical (P<0.0001) and inferior (P=0.03) regions.Conclusion A single oral dose of amitriptyline can induce changes in the uptake and retention of cardiac MIBG, indicating the feasibility of use of pharmacological intervention in cardiac neurotransmission imaging.     

Fludarabine-induced apoptosis in CD19+/CD5+B-CLL cells is a direct and nurse-like-cell independent effect

B-cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy characterized by the accumulation of mature CD5+ B lymphocytes with a defective apoptosis. A subset of blood monocyte-derived adherent cells generated in vitro protects B-CLL cells from apoptosis playing a role as nurse-like cells (NLCs). Fludarabine (9-beta-D-arabinofuranosyl-2-fluoroadenine; F-ara-A) is an adenine nucleoside analog used to treat B-CLL. To gain insight into the mechanisms implicated in the antitumoral effect of fludarabine in B-CLL cells, we performed cross-cultures with B-CLL cells and NLCs treated and untreated with fludarabine. Our results showed that fludarabine blocked the development of NLCs and induced apoptosis in these cells when they were present in culture. Moreover, CD19+/CD5+B-CLL cells treated with fludarabine underwent apoptosis and this event was not related with the presence of NLCs whether treated or not with fludarabine. In conclusion, apoptosis induced by fludarabine in CD19+/CD5+B-CLL cells was due to a direct effect on these cells and not due to its effect in the NLCs.