Medial tunica degeneration of the ascending aortic wall is associated with specific microRNA changes in bicuspid aortic valve disease

Ascending aortic diameter is not an accurate parameter for surgical indication in patients with bicuspid aortic valve (BAV). Thus, the present study aimed to identify specific microRNAs (miRNAs/miRs) and their expression levels in aortic wall aneurysm associated with BAV according to severity of medial degeneration and to elucidate the association between the tissue expression levels of the miRNAs with their expression in plasma. Aortic wall and blood specimens were obtained from 38 patients: 12 controls and 26 patients with BAV with ascending aortic aneurysm. Of the patients with BAV, 19 had cusp fusions of right and left, 5 of right and non-coronary, and 2 of left and non-coronary. Two groups of patients were identified according to the grade of medial degeneration (MD): Low-grade D group (LGMD) and high-grade MD group (HGMD). Expression level of miR-122, miR-130, miR-718 and miR-486 were validated by reverse transcription-quantitative PCR in plasma and tissue samples. MD grade was found to be independent from the BAV phenotype. The HGD group showed increased expression levels of MMP-9 and MMP-2, and an increase in the number of apoptotic cells. Tissue expression levels of miR-718 and miR-122 were lower in the LGMD and HGD groups compared with expression in the control group; the HGD group showed increased levels of miR-486. Plasma expression levels of miR-122 were decreased in the LGMD and HGD groups, and miR-718 was only reduced in the HGD group. On the contrary, expression of miR-486 was increased in the LGMD and HGD groups. The data suggested that miR-486 may be considered as a non-invasive biomarker of aortic wall degeneration. Dysregulation of this putative biomarker may be associated with high risk of dissection and rupture in patients with BAV

The AGILE Mission

AGILE is an Italian Space Agency mission dedicated to observing the gamma-ray Universe. The AGILE's very innovative instrumentation for the first time combines a gamma-ray imager (sensitive in the energy range 30 MeV-50 GeV), a hard X-ray imager (sensitive in the range 18-60 keV), a calorimeter (sensitive in the range 350 keV-100 MeV), and an anticoincidence system. AGILE was successfully launched on 2007 April 23 from the Indian base of Sriharikota and was inserted in an equatorial orbit with very low particle background. Aims. AGILE provides crucial data for the study of active galactic nuclei, gamma-ray bursts, pulsars, unidentified gamma-ray sources, galactic compact objects, supernova remnants, TeV sources, and fundamental physics by microsecond timing. Methods. An optimal sky angular positioning (reaching 0.1 degrees in gamma- rays and 1-2 arcmin in hard X-rays) and very large fields of view (2.5 sr and 1 sr, respectively) are obtained by the use of Silicon detectors integrated in a very compact instrument. Results. AGILE surveyed the gamma- ray sky and detected many Galactic and extragalactic sources during the first months of observations. Particular emphasis is given to multifrequency observation programs of extragalactic and galactic objects. Conclusions. AGILE is a successful high-energy gamma-ray mission that reached its nominal scientific performance. The AGILE Cycle-1 pointing program started on 2007 December 1, and is open to the international community through a Guest Observer Program

Treatment of metastatic breast cancer with vinorelbine and docetaxel

OBJECTIVE: A phase II study was performed to evaluate efficacy and safety of the combination vinorelbine and docetaxel in patients with metastatic breast cancer previously treated with anthracycline-based regimens. Overall 41 patients were included in the study. METHODS: Treatment consisted of vinorelbine 25 mg/m and docetaxel 75 mg/m, both administered on day 1 every 3 weeks for a maximum of 9 cycles. Most patients (92%) were postmenopausal with a median age of 57 years, and median ECOG performance of 1. Sites of disease were viscera in 42% of patients, bones in 30%, soft-tissues in 32%. Sixty-five percent of patients had >2 metastatic sites. Previous treatments included neo-adjuvant chemotherapy in 7.3% of cases, adjuvant chemotherapy in 71%, and front-line chemotherapy for advanced disease in 50% of cases. RESULTS: A total of 273 cycles of chemotherapy were delivered (mean 6 cycles/patient). All patients were assessable for toxicity: alopecia was recorded in all patients, grade 2-3 neutropenia in 34% and grade 4 in 9.7%; grade 2-3 nausea/vomiting in 29%, grade 2-3 mucositis in 24.3%. Out of 39 patients evaluable for response, 7 (18%) complete responses and 13 (33%) partial responses have been recorded with an overall response rate of 51%. Six patients (15%) experienced stable disease and 13 patients (33%) progressed. Mean duration of responses was 15.2 months. Median time to progression and median overall survival were 6.2 and 14 months, respectively. CONCLUSION: In patients with metastatic breast cancer previously treated with anthracyclines the combination vinorelbine-docetaxel is very active and well tolerated representing a valid therapeutic option for the management of this patient populatio

Activity and toxicity of oxaliplatin plus raltitrexed in 5-fluorouracil refractory metastatic colorectal adeno-carcinoma

Background: This study evaluated the antitumor efficacy and safety of a novel oxaliplatin/raltitrexed combination in pretreated advanced colorectal cancer patients. Patients and Methods: Forty-five patients with 5-fluorouracil-refractory metastatic colorectal cancer received raltitrexed 3.0 mg/m2 as a 15-minute intravenous (i.v.) infusion, followed 45 min later by l-OHP 130mg/m2 iv as 2-h venous infusion on 1 day every 3 weeks. All patients had histologically proven metastatic colorectal cancer, age 18-75, measurable disease and normal baseline biological values. Most patients (60%) had >2 disease sites. All patients were assessed for safety and also for response according to an intent-to-treat fashion. Results: The overall response rate was 29% (95% CL 16%-44%) including one CR (2%) and 12 PR (27%). Six patients (16%) showed a stabilization of disease for a tumor growth control rate of 45%. The median time to progression was 4 months (range 1-12+) and median overall survival was 9 months (range 1-29+). Conclusion: These data confirm that this oxaliplatin/raltitrexed combination is effective against metastatic colorectal carcinoma, well tolerated with low grade toxicity and easy to administrer. Further evaluation of this regimen seems warranted as an alternative to fluoropyrimidine-based combinations

A phase i-II study of cyclophosphamide, epidoxorubicin, levofolinic acid/5-fluorouracil and recombinant human granulocyte colony stimulating factor in metastatic breast carcinoma

Thirty patients with measurable metastatic breast carcinoma were treated with a combination of cyclophosphamide 600 mg/m2 on day 1, levofolinic acid 100 mg/m2 plus 5-fluorouracil 375 mg/m2 on days 1-3, and epidoxorubicin (EDXR) in three refracted doses on days 1-3 with G-CSF rescue for 10 days. In the phase I part of the study, groups of 3 patients received EDXR 20, 25, 30, 35, and 40 mg/m2/day until the dose limiting toxicity (DLT) was reached. At the dose of 40mg/m2/day prolonged grade 4 leukopenia, severe proctitis, and grade 3 diarrhea represented the DLT. All subsequent partients were treated at the maximal tolerated dose of EDXR (35 mg/m2/day). In the group of 18 patients treated at 35 mg/m2/day the overall response rate was 78% with 22% CR and 56% PR. Four patients did not respond. Objective responses were seen at all tumor sites including bone and viscera, which usually are rather chemotherapy insensitive. Toxicity was generally acceptable. Although the response rate was quite high, the duration of objective tumor regression and patients' survival were not impressive. In conclusion, we do not recommend routine use of such an aggressive regimen for palliation of advanced breast cancer. Results of the present and similar studies may, however, be useful for planning of neoadjuvant or adjuvant trials with curative intent. ©1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Malignant fibrous histiocytoma of the gallbladder: case report and review of the literature

Malignant fibrous histiocytoma is a soft tissue sarcoma of mesenchymal origin. It can rarely present as a primary gallbladder tumor with only five cases having been reported to date in the English literature. Here we report the sixth documented case of malignant fibrous histiocytoma of the gallbladder, and we review all other cases reported. The outcome of the visceral sarcomas is poor when compared with tumors arising from the soft tissues. The treatment of primary malignant fibrous histiocytomas of the gallbladder is surgery. However, tumor recurrence is the norm even if wide clean margins are obtained. In contrast to tumors arising from the extremities the role of adjuvant radiotherapy and chemotherapy is less clear in the case of retroperitoneal and visceral sarcomas. Our patient is still alive and free of disease 46 weeks after surgery. The fact that this is the longest survival reported to date underscores the dismal prognosis of this disease

Medial tunica degeneration of the ascending aortic wall is associated with specific microRNA changes in bicuspid aortic valve disease

Ascending aortic diameter is not an accurate parameter for surgical indication in patients with bicuspid aortic valve (BAV). Thus, the present study aimed to identify specific microRNAs (miRNAs/miRs) and their expression levels in aortic wall aneurysm associated with BAV according to severity of medial degeneration and to elucidate the association between the tissue expression levels of the miRNAs with their expression in plasma. Aortic wall and blood specimens were obtained from 38 patients: 12 controls and 26 patients with BAV with ascending aortic aneurysm. Of the patients with BAV, 19 had cusp fusions of right and left, 5 of right and non-coronary, and 2 of left and non-coronary. Two groups of patients were identified according to the grade of medial degeneration (MD): Low-grade D group (LGMD) and high-grade MD group (HGMD). Expression level of miR-122, miR-130, miR-718 and miR-486 were validated by reverse transcription-quantitative PCR in plasma and tissue samples. MD grade was found to be independent from the BAV phenotype. The HGD group showed increased expression levels of MMP-9 and MMP-2, and an increase in the number of apoptotic cells. Tissue expression levels of miR-718 and miR-122 were lower in the LGMD and HGD groups compared with expression in the control group; the HGD group showed increased levels of miR-486. Plasma expression levels of miR-122 were decreased in the LGMD and HGD groups, and miR-718 was only reduced in the HGD group. On the contrary, expression of miR-486 was increased in the LGMD and HGD groups. The data suggested that miR-486 may be considered as a non-invasive biomarker of aortic wall degeneration. Dysregulation of this putative biomarker may be associated with high risk of dissection and rupture in patients with BAV

Weekly paclitaxel, 5-fluorouracil and folinic acid with granulocyte colony-stimulating factor support in metastatic breast cancer patients: a phase II study

We conducted a phase II study to determine the activity and tolerability of weekly paclitaxel, 5-fluorouracil (5-FU) and folinic acid plus granulocyte colony-stimulating factor (G-CSF) support in anthracycline-pre-treated or -resistant metastatic breast cancer patients. The phase II study was designed following the Simon optimal-two stage method. Patients received paclitaxel 80 mg/m, folinic acid 10 mg/m and bolus infusion of 5-FU 300 mg/m every week plus G-CSF on day 3 for 24 consecutive weeks in the absence of disease progression. From May 1998 to May 2000, 51 patients entered the study. Patients received a median relative dose intensity of 97.5% (range 81-100%). No severe toxicities were observed. Seven patients (14%) experienced neutropenia grade 2. Seven patients (14%) experienced grade 2 anemia. Two patients (4%) experienced severe asthenia. Three out of 50 evaluable patients [6%, 95% confidence interval (CI) 2-12.6%] showed a complete response, whereas 23 (46%, 95% CI 32.2-59.8%) had a partial response, with an overall response rate of 52% (95% CI 38.2-65.8%). In addition, eight patients (15.7%) had stable disease. In the 13 patients untreated for metastatic disease, the overall response rate was 92.3% (CI 77.8-100), with one complete response and 11 partial responses (84.6% CI 65-100%). In the whole group, the median time to progression and overall survival were 8 (range 1-18) and 14 months (95% CI 11-17), respectively. Thus, in metastatic breast cancer patients pre-treated with anthracyclines, the weekly administration of paclitaxel, 5-FU and folinic acid with G-CSF support seems to be extremely tolerable and active