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Costanzo S.,IRCCS Instituto Neurologico Mediterraneo Neuromed | De Curtis A.,IRCCS Instituto Neurologico Mediterraneo Neuromed | Di Niro V.,Nuovo Ospedale Civile di Sassuolo | Olivieri M.,EPICOMED Research Srl | And 9 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2015

Objective Postoperative atrial fibrillation is a major cause of morbidity and mortality for stroke after cardiac surgery. Both systemic inflammation and oxidative stress play a role in the initiation of postoperative atrial fibrillation after cardiac surgery. The possible association between long-term intake of antioxidant-rich foods and postoperative atrial fibrillation incidence was examined in patients undergoing cardiac surgery. Methods A total of 217 consecutive patients (74% were men; median age, 68.4 years) undergoing cardiac surgery, mainly coronary artery bypass grafting and valve replacement or repair, were recruited from January 2010 to September 2012. Total antioxidant capacity was measured in foods by the Trolox equivalent antioxidant capacity assay. The European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire was used for dietary total antioxidant capacity assessment. The association among tertiles of dietary total antioxidant capacity and postoperative atrial fibrillation incidence was assessed using multivariable logistic analysis. Results The overall incidence of total arrhythmias and postoperative atrial fibrillation was 42.4% and 38.2%, respectively. In multivariable analysis, after adjustment for age, gender, use of hypoglycemic drugs, physical activity, education, previous diagnosis of atrial fibrillation, and total energy intake, patients in the highest tertile of dietary total antioxidant capacity had a lower risk of postoperative atrial fibrillation than patients in the 2 lowest tertiles (odds ratio, 0.46; 95% confidence interval, 0.22-0.95; P =.048). A restricted cubic spline transformation confirmed the nonlinear relationship between total antioxidant capacity (in continuous scale) and postoperative atrial fibrillation (P =.023). When considering only coronary artery bypass grafting, valve replacement/repair, and combined surgeries, the protective effect on postoperative atrial fibrillation of a diet rich in antioxidants was confirmed. Conclusions Long-term consumption of antioxidant-rich foods is associated with a reduced incidence of postoperative atrial fibrillation in patients undergoing cardiac surgery. © 2015 The American Association for Thoracic Surgery.


Cellini F.,Policlinico Universitario Campus Bio Medico | Morganti A.G.,Fondazione di Ricerca e Cura Giovanni Paolo II | Morganti A.G.,Catholic University of the Sacred Heart | Di Matteo F.M.,Biomedical University of Rome | And 2 more authors.
Radiation Oncology | Year: 2014

Gastroesophageal cancers (such as esophageal, gastric and gastroesophageal-junction -GEJ- lesions) are worldwide a leading cause of death being relatively rare but highly aggressive. In the past years, a clear shift in the location of upper gastrointestinal tract tumors has been recorded, both affecting the scientific research and the modern clinical practice. The integration of pre- or peri-operative multimodal approaches, as radiotherapy and chemotherapy (often combined), seems promising to further improve clinical outcome for such presentations. In the past, the definition of GEJ led to controversies and confusion: GEJ tumors have been managed either grouped to gastric or esophageal lesions, following slightly different surgical, radiotherapeutic and systemic approaches. Recently, the American Joint Committee on Cancer (AJCC) changed the staging and classification system of GEJ to harmonize some staging issues for esophageal and gastric cancer. This review discusses the most relevant historical and recent evidences of neoadjuvant treatment involving Radiotherapy for GEJ tumors, and describes the efficacy of such treatment in the frame of multimodal integrated therapies, from the new point of view of the recent classification of such tumors. © 2014 Cellini et al.; licensee BioMed Central Ltd.


Picardi V.,Fondazione di Ricerca e Cura Giovanni Paolo II | Deodato F.,Fondazione di Ricerca e Cura Giovanni Paolo II | Guido A.,University of Bologna | Giaccherini L.,University of Bologna | And 14 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2016

Purpose The management of patients with symptomatic rectal cancer not amenable to curative treatment may be challenging. The aim of this phase 2 study was to evaluate the efficacy of short-course radiation therapy in patients with obstructing rectal cancer. Methods and Materials Patients who were not candidates for surgical resection because of synchronous metastases, age, and/or comorbidities were considered eligible. The sample size was calculated based on the 2-stage design of Simon. Short-course radiation therapy was delivered with an isocentric 4-field box technique (total, 25 Gy; 5 fractions in 5 days). Chemotherapy was suspended during radiation treatment. Clinical outcome measures were symptomatic response rate, toxicity, colostomy-free survival, and overall survival. Results From October 2003 to November 2012, 18 patients (median age, 77.5 years) were enrolled. The median follow-up was 11.5 months (range, 3-36 months). Four weeks after treatment, a complete response (ie, complete symptom resolution) was observed in 38.9% of patients and a partial response in 50.0% cases, whereas 11.1% had no response. The rates of reduction or resolution of pain and bleeding were 87.5% and 100%, respectively. The 1-, 2-, and 3-year colostomy-free survival rates were 100%, 71.4%, and 47.6%, respectively (median, 30 months). The 1-, 2-, and 3-year cumulative overall survival rates were 85.2%, 53%, and 39.8%, respectively (median, 25 months). No patients stopped treatment because of gastrointestinal or genitourinary toxicities: 38.9% of patients had grade 1 to 2 toxicity, and 16.7% had grade 3 toxicity. Only 1 patient had hematologic grade 2 toxicity, and 2 patients had grade 2 skin toxicity. Conclusions Short-course radiation therapy may represent a safe and effective alternative treatment option in patients with obstructing rectal cancer not eligible for curative treatment, allowing colostomy to be avoided in a substantial proportion of patients. © 2016 Elsevier Inc.


Grafone T.,Fondazione di Ricerca e Cura Giovanni Paolo II | Palmisano M.,Vita-Salute San Raffaele University | Nicci C.,Fondazione di Ricerca e Cura Giovanni Paolo II | Storti S.,Fondazione di Ricerca e Cura Giovanni Paolo II
Oncology Reviews | Year: 2012

Hematopoiesis, the process by which the hematopoietic stem cells and progenitors differentiate into blood cells of various lineages, involves complex interactions of transcription factors that modulate the expression of downstream genes and mediate proliferation and differentiation signals. Despite the many controls that regulate hematopoiesis, mutations in the regulatory genes capable of promoting leukemogenesis may occur. The FLT3 gene encodes a tyrosine kinase receptor that plays a key role in controlling survival, proliferation and differentiation of hematopoietic cells. Mutations in this gene are critical in causing a deregulation of the delicate balance between cell proliferation and differentiation. In this review, we provide an update on the structure, synthesis and activation of the FLT3 receptor and the subsequent activation of multiple downstream signaling pathways. We also review activating FLT3 mutations that are frequently identified in acute myeloid leukemia, cause activation of more complex downstream signaling pathways and promote leukemogenesis. Finally, FLT3 has emerged as an important target for molecular therapy. We, therefore, report on some recent therapies directed against it. © Copyright T. Grafone et al., 2012.


Pierro A.,Fondazione di Ricerca e Cura Giovanni Paolo II | Restaino G.,Fondazione di Ricerca e Cura Giovanni Paolo II | Missere M.,Fondazione di Ricerca e Cura Giovanni Paolo II | Maselli G.,Fondazione di Ricerca e Cura Giovanni Paolo II | And 2 more authors.
Gazzetta Medica Italiana Archivio per le Scienze Mediche | Year: 2013

A 70-year-old man with plasmablastic lymphoma underwent skeletal survey that documented the presence of multiple osteolytic bone lesions in the left tibia, skull and forearm, finding not common in this disease. Radiographs of the cervical spine showed an abnormal appearance of the arch of the atlas with the presence of a posterior bone fragment, located cranial to the spinous process of epistropheus. This morphological abnormality, although suspected to anatomical variation, we were not allowed, only with the X-ray examination, to exclude the presence of osteolytic bone changes at that level, so the patient underwent magnetic resonance imaging (MRI) and computed tomography (CT) of the cervical spine. CT confirmed the congenital abnormality, while MRI has ruled out changes in the spinal cord. This anatomical variation, uncommon, poses problems of differential diagnosis to radiographic examination alone, in patients with multiple osteolytic lesions or even in patients who have suffered trauma, and therefore know the typical appearance of this anatomical variation, and as it presents itself in various modes imaging is of paramount importance both for the radiologist and for the clinician. Furthermore, this case shows an uncommon finding for plasmablastic lymphoma that is, multiple osteolytic lesions.


PubMed | Fondazione di Ricerca e Cura Giovanni Paolo II and Vita-Salute San Raffaele University
Type: Journal Article | Journal: Oncology reviews | Year: 2015

Hematopoiesis, the process by which the hematopoietic stem cells and progenitors differentiate into blood cells of various lineages, involves complex interactions of transcription factors that modulate the expression of downstream genes and mediate proliferation and differentiation signals. Despite the many controls that regulate hematopoiesis, mutations in the regulatory genes capable of promoting leukemogenesis may occur. The FLT3 gene encodes a tyrosine kinase receptor that plays a key role in controlling survival, proliferation and differentiation of hematopoietic cells. Mutations in this gene are critical in causing a deregulation of the delicate balance between cell proliferation and differentiation. In this review, we provide an update on the structure, synthesis and activation of the FLT3 receptor and the subsequent activation of multiple downstream signaling pathways. We also review activating FLT3 mutations that are frequently identified in acute myeloid leukemia, cause activation of more complex downstream signaling pathways and promote leukemogenesis. Finally, FLT3 has emerged as an important target for molecular therapy. We, therefore, report on some recent therapies directed against it.


PubMed | Fondazione di Ricerca e Cura Giovanni Paolo II
Type: Journal Article | Journal: Thrombosis research | Year: 2012

The renin-angiotensin system (RAS) promotes angiogenesis and growth of neoplastic cells. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor AT1 blockers may protect against cancer. Tissue factor (TF), for its involvement in tumor growth, angiogenesis, and metastasis is considered a hallmark of cancer progression. In this study we evaluated whether RAS blockade modulates TF constitutive expression by the metastatic breast carcinoma MDA-MB-231 cell line.Cell TF activity was assessed by one stage clotting time, TF and VEGF antigens and mRNA levels by ELISA and RT-PCR, respectively. AT(1) was detected by flow-cytometry and angiotensin-II levels by EIA.Captopril reduced in a concentration-dependent way both the strong constitutive TF activity (983.255.2 vs. 686.7135.1U/510(5) cells with 10g/ml captopril) and antigen (32.35.9 vs. 13.26.6ng/ml) in MDA-MB-231. Similar results were observed with enalapril. AT1 was present on cell membrane and losartan, a competitive inhibitor of AT1, reduced TF expression to a degree similar as that exerted by ACE inhibitors. Moreover, captopril and losartan downregulated the constitutive mRNA TF expression by ~35%. Similar results were observed with anti-AT1 and angiotensin II antibodies. In addition, the constitutive VEGF antigen and mRNA levels were reduced in the presence of captopril or losartan, and an anti-VEGF antibody downregulated cell TF activity by ~40%.These results could, at least in part, contribute to the discussion about the possible effects of ACE inhibitors and AT1 receptor antagonists in malignancy, and offer new clues to support their use for tumor control.


PubMed | Fondazione di Ricerca e Cura Giovanni Paolo II
Type: | Journal: Journal of clinical imaging science | Year: 2012

We report a case of penile metastases from recurrent prostatic adenocarcinoma that was the first sign of a widespread metastatic disease in the absence of any increase in prostate-specific antigen (PSA) level. In April 2011, an 80-year-old man presented to our Radiotherapy Unit with multiple palpable hard nodules in the penis, dysuria, and moderate perineal pain, 7 years after he had received radiotherapy for prostate cancer. Nodules in the penis had appeared in February 2011. The ultrasound and magnetic resonance (MR) imaging suggested the diagnosis of multiple penile metastases. A total body computed tomography scan revealed a systemic spread of the disease, with multiple metastases in the liver, bones, and lungs. PSA level was 0.126 ng/ml. A fine needle aspiration biopsy of the liver lesion was undertaken, and the histopathologic examination revealed the prostatic origin of the metastases, so androgen deprivation therapy was started. The diagnosis of metastases should be considered in a patient with prior history of prostate malignancies presenting with solid nodules in the penis, even if the PSA level is low.

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