Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors latent in the cytoplasm that participate in normal cellular events, such as differentiation, proliferation, cell survival,... more
Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors latent in the cytoplasm that participate in normal cellular events, such as differentiation, proliferation, cell survival, apoptosis, and angiogenesis following cytokine, growth factor, and hormone signaling. STATs are activated by tyrosine phosphorylation, which is normally a transient and tightly regulates process. Nevertheless, several constitutively activated STATs have been observed in a wide number of human cancer cell lines and primary tumors, including blood malignancies and solid neoplasias. STATs can be divided into two groups according to their specific functions. One is made up of STAT2, STAT4, and STAT6, which are activated by a small number of cytokines and play a distinct role in the development of T-cells and in IFNgamma signaling. The other group includes STAT1, STAT3, and STAT5, activated in different tissues by means of a series of ligands and involved in ...
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Liposarcoma (LPS) is the most common soft tissue sarcoma. It has been demonstrated that mir-155 was the most overexpressed miRNA in well-differentiated LPS(WDLPS)/dedifferentiated LPS (DDLPS). The aim of this study is to evaluate the... more
Liposarcoma (LPS) is the most common soft tissue sarcoma. It has been demonstrated that mir-155 was the most overexpressed miRNA in well-differentiated LPS(WDLPS)/dedifferentiated LPS (DDLPS). The aim of this study is to evaluate the involvement of Dicer, Drosha and mir-155 in development of LPS and their possible role in stratification of different histological subtypes. Dicer, Drosha and mir-155 mRNA levels were analyzed in formalin-fixed paraffin-embedded specimens from patients diagnosed with 62 LPS and compared with samples of adipose tissues of healthy donors. The experimental data were obtained using qRT-PCR comparing Dicer, Drosha and mir-155 expression levels in tumor samples versus normal fat. The tumor samples from LPS patients showed a significantly lower Dicer expression versus normal adipose tissue, while Drosha levels did not differ. Concerning mir155 expression levels, our results demonstrated a significant mir-155 up-regulation in all LPS subtypes versus normal adip...
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The last few decades have witnessed a silent revolution in the war against NSCLC, thanks to the discovery of "oncogenic drivers" and the subsequent development of targeted therapies. The discovery of the EML4-ALK fusion gene in... more
The last few decades have witnessed a silent revolution in the war against NSCLC, thanks to the discovery of "oncogenic drivers" and the subsequent development of targeted therapies. The discovery of the EML4-ALK fusion gene in a subgroup of patients with NSCLC and the subsequent clinical development of crizotinib has been an amazing success story in lung cancer translational-research, and its accelerated approval [only 4 years from the discovery of ALK rearrangement in NSCLC to the approval by the Food and Drug Administration (FDA)] marked the beginning of the new decade of targeted therapy. However, common to all targeted therapies, despite an initial benefit, patients inevitably experience tumor progression, due to the development of resistance. Several molecular mechanisms are responsible for acquired resistance, such as secondary mutations of ALK kinase domain or amplification of ALK fusion gene, or the activation of other oncogenic drivers, which may cause resistance...
We evaluated the role of residual vein thrombosis (RVT) to assess the optimal duration of anticoagulants in patients with cancer who have deep vein thrombosis (DVT) of the lower limbs. Patients with active cancer and a first episode of... more
We evaluated the role of residual vein thrombosis (RVT) to assess the optimal duration of anticoagulants in patients with cancer who have deep vein thrombosis (DVT) of the lower limbs. Patients with active cancer and a first episode of DVT treated with low molecular weight heparin (LMWH) for 6 months were eligible. Patients were managed according to RVT findings: those with RVT were randomly assigned to continue LMWH for an additional 6 months (group A1) or to discontinue it (group A2), and patients without RVT stopped LMWH (group B). The primary end point was recurrent venous thromboembolism (VTE) during the 1 year after disconinuation of LMWH, and the secondary end point was major bleeding. Analyses are from the time of random assignment. Between October 2005 and April 2010, 347 patients were enrolled. RVT was detected in 242 patients (69.7%); recurrence occurred in 22 of the 119 patients in group A1compared with 27 of 123 patients in group A2. The adjusted hazard ratio (HR) for g...
Research Interests: Treatment Outcome, Prospective studies, Humans, Female, Male, and 15 moreClinical oncology, cerebral Venous sinus thrombosis, Follow-up studies, Anticoagulants, Risk factors, Recurrence, Aged, Middle Aged, Time Factors, Survival Rate, Neoplasms, Disease Progression, Risk Factors, Venous thromboembolism, and Lower Extremity
Many targeted drugs have been studied to target the molecular pathways involved in the development of gastrointestinal cancers. Anti-VEGF, anti-EGFR agents, and recently also multi-kinase inhibitor regorafenib, have already been available... more
Many targeted drugs have been studied to target the molecular pathways involved in the development of gastrointestinal cancers. Anti-VEGF, anti-EGFR agents, and recently also multi-kinase inhibitor regorafenib, have already been available for the treatment of metastatic colorectal cancer patients. To date, Her-2 positive, gastric cancer patients, are also treated with trastuzumab, while the multi-targeted inhibitor, sorafenib, represents the standard treatment for hepatocellular carcinoma patients. Finally, sunitinib and everolimus, have been approved for the treatment of the neuroendocrine gastroenteropancreatic tumors. Actually a great number of further drugs are under preclinical and clinical development. The aim of this review is to provide a comprehensive overview of the state of art, focusing on the new emerging strategies in the personalized treatment of gastrointestinal tumors.
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A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction... more
A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF were associated with tumor-node-metastasis (TNM) stage and node status, whereas only DNA ploidy was related to depth of invasion. CB, CL, uPA, but not CD, levels were significantly higher in GC as compared to paired normal mucosa, whereas stefin A levels were lower in tumor tissues. CB levels were ...
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We investigated the relationships between risk of colon and rectal cancers and physical activity in both sexes at different ages by a case-control study conducted between 1991 and 1996 in six Italian centres. Cases were 1225 patients (688... more
We investigated the relationships between risk of colon and rectal cancers and physical activity in both sexes at different ages by a case-control study conducted between 1991 and 1996 in six Italian centres. Cases were 1225 patients (688 men, 537 women) below the age of 75 with colon cancer and the controls included 4154 patients (2073 men, 2081 women) admitted to hospital for acute, non-neoplastic conditions. We also analysed 722 cases of rectal cancer. Compared with the lowest level of occupational physical activity at 30-39 years old the odds ratios (OR) for the highest level were 0.64 (95% confidence interval, CI 0.44-0.93) in men and 0.49 (95% CI 0.33-0.72) in women. The inverse association in both sexes was similar at 15-19 and 50-59 years old. No association was found in either sex for leisure-time physical activity. For both sexes the inverse relationship between occupational physical activity at 30-39 years old and colon cancer risk was not significantly heterogeneous acro...
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Cathepsin D content and activity were determined in matched paired sets of colorectal tumor tissue and normal mucosa and correlated with a number of biological and clinical parameters. Significantly higher cathepsin D activity was... more
Cathepsin D content and activity were determined in matched paired sets of colorectal tumor tissue and normal mucosa and correlated with a number of biological and clinical parameters. Significantly higher cathepsin D activity was measured in tumor cytosol compared to paired normal mucosa (p < 0.02), in Dukes' stage A tumors compared to Dukes' B and C (p < 0.05), in tumors < 5 cm compared to those > 5 cm, or in tumors with a low proliferation rate compared to those with a high proliferation rate (p < 0.05). Moreover, significant differences in enzyme activity between tumor tissue and paired normal mucosa were observed in node-positive and G2 tumors (p < 0.05). No significant correlation between cathepsin D activity and other biological parameters was found. Further, no differences in cathepsin D content between tumor tissue and paired normal mucosa were observed except in Dukes' stage A tumors (p < 0.02). A significantly increased cathepsin D content...
Research Interests: Oncology, Linear models, Humans, Intestinal Mucosa, cathepsin D, and 6 moreFemale, Male, Aged, Middle Aged, Adult, and Colorectal Neoplasms
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Some clinical studies that were performed for the purpose of assessing the potential cardiotoxicity of mitoxantrone (DHAD) have shown that repeated administrations of the drugs in some patients cause a mild impairment of cardiac functions... more
Some clinical studies that were performed for the purpose of assessing the potential cardiotoxicity of mitoxantrone (DHAD) have shown that repeated administrations of the drugs in some patients cause a mild impairment of cardiac functions and morphological changes in the myocardial cells qualitatively similar to those elicited by anthracyclines. Since doxorubicin has been reported to cause acute cardiac effects, probably related to its chronic cardiotoxicity, experiments were carried out on the rabbit heart to investigate whether DHAD is also able to induce acute cardiac effects. Our results show that this drug caused a reversible dose-related impairment of cardiac contractility on the isolated and perfused rabbit heart while it was not able to induce ECG alterations in normal rabbits. These findings demonstrate that in the rabbit DHAD induces an acute cardiac activity qualitatively similar to that of doxorubicin and suggest that this animal model could be a useful tool to study the...
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In the past decade, the advent of targeted therapy led to a silent revolution in the war against lung cancer and a significant evolution on the concept of Phase I clinical trials design. Thanks to the specificity of their target, the new... more
In the past decade, the advent of targeted therapy led to a silent revolution in the war against lung cancer and a significant evolution on the concept of Phase I clinical trials design. Thanks to the specificity of their target, the new drugs have radically changed NSCLC treatment, leading to the development of personalized strategies. The accelerated approval of the first ALK-inhibitor, Crizotinib and more recently Ceritinib, without a Phase III randomized, clinical trial, has been an amazing success story in lung cancer research, marking the beginning of a new decade of targeted drugs development, characterized by modern, biomarker-driven, early clinical trial design and shorter times for clinical approval. Is Ceritinib a new panacea for the treatment of ALK-rearranged NSCLC? We aimed to discuss the reasons of such success, including the new emerging questions, regarding mechanisms of acquired resistance, and the best treatment algorithm for ALK-rearranged NSCLC patients.
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Background: In a population-based multicenter case-control study of diet, life-style, and gastric cancer a large series of adults, aged 30–75 years (mean 58.9 yearss), were randomly sampled from the general population in 3 areas of... more
Background: In a population-based multicenter case-control study of diet, life-style, and gastric cancer a large series of adults, aged 30–75 years (mean 58.9 yearss), were randomly sampled from the general population in 3 areas of Central-Northern Italy. Aim of the study: To evaluate the relationship between plasma levels of antioxidant vitamins and cholesterol, and sociodemographic characteristics, life-style factors, and dietary
Research Interests: Nutrition and Dietetics, Life Style, Diet, Vitamins, Carotenoids, and 29 moreSocial Class, Multivariate Analysis, Italy, Antioxidants, Vitamin A, Humans, Smoking, Cholesterol, Chronic Disease, Female, Gastric Cancer, Blood sampling, Alcohol Drinking, Male, Vitamin E, Body Mass Index, Alcohol Consumption, High Pressure Liquid Chromatography, Aged, Middle Aged, Questionnaires, Ascorbic Acid, Adult, Covariance analysis, Case Control Study, General Population, Case Control Studies, Nutrient Intake, and Dietary Habits
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Introduction: The therapeutic options for NSCLC are limited barring targeted drugs, such as EGFR tyrosine-kinase inhibitors and anaplastic lymphoma kinase inhibitors, for patients bearing oncogenic mutations. Platinum-based chemotherapy... more
Introduction: The therapeutic options for NSCLC are limited barring targeted drugs, such as EGFR tyrosine-kinase inhibitors and anaplastic lymphoma kinase inhibitors, for patients bearing oncogenic mutations. Platinum-based chemotherapy remains the best strategy for most patients. New targeted drugs, including mAbs and small molecules, are currently under clinical investigation for treating NSCLC patients. Areas covered: The authors of this article focus on farletuzumab , a mAb targeting folate receptor, which has been studied in ovarian cancer and various other malignancies. In this review, the authors review its potential as therapy for NSCLC, because of the biological rationale provided by the expression of folate receptor α in most of lung adenocarcinoma. The authors provide details of farletuzumab&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s mechanism of action and discuss the results from completed Phase I and Phase II clinical trials. They also highlight ongoing trials. Expert opinion: There are an increasing number of treatment options for NSCLC and it is hoped that farletuzumab could be added to them. That being said, further evidence for its use with NSCLC patients is still needed. It could have a synergic effect with pemetrexed, because these two drugs have a similar target, namely the folate pathway. This combined action could provide an improved efficacy, although there are some concerns about increased toxicity. However, the authors do note that the combination of farletuzumab with other cytotoxic drugs has not been shown to increase toxicity alone.
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Research Interests: Time Series, Environmental Health, Spline smoothing and regression, Public Health, Risk assessment, and 30 moreAdolescent, Cardiovascular disease, Social Class, Seasonality, Humans, Child, Europe, Female, Male, Infant, Weather, High Temperature, Newborn Infant, Temperature measurement, Aged, Middle Aged, International Classification of Diseases, Adult, Time Factors, General Linear Model, Urban Population, Risk Assessment, Socio Economic Status, Health Effect, Vital statistics, Environmental, Poisson Distribution, Age Groups, Air Pollutants, and Relative Risk
Accurate assessment of intestinal complications of... more
Accurate assessment of intestinal complications of Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (CD) is extremely important, both in clinical practice and in trials. The accuracy of radiographic and ultrasonographic diagnosis of internal fistulae and abscesses complicating CD is still debated and requires further investigation. We compared ultrasonography (US) and contrast radiography in detecting intestinal fistulae and abscesses complicating CD. A prospective study was carried out on 625 consecutive CD patients who underwent complete evaluation of the intestinal tract by means of colonoscopy and double contrast barium enema, small bowel enteroclysis, and abdominal ultrasound (US). Computed tomography (CT) was also carried out in cases of severe CD with clinical suspicion of septic complications. The accuracy of US, barium radiology, and CT in detecting internal fistulae and abscesses was assessed by comparing results with intraoperative findings in 128 consecutive patients who underwent operation immediately after diagnostic workup. Internal fistulae and intra-abdominal abscesses were identified intraoperatively in 56 (43.7%) and 26 (20.3%) patients, respectively. Diagnostic accuracy of US and x-ray studies in detecting internal fistulae was comparable (85.2% vs 84.8%), with sensitivity of 71.4% for US and 69.6% for x-ray studies, and specificity of 95.8% for both. Combination of radiographic techniques and US significantly improved diagnostic accuracy in detection of internal fistulae. In severe cases of CD with clinical suspicion of septic complications such as abdominal mass or fever, the accuracy of US, barium studies, and CT was 88.5%, 80.3%, and 77%, respectively (p = ns). The presence of abscesses was correctly detected in 90.9% of cases by means of US and in 86.4% by CT (p = ns), although accuracy was higher for CT (91.8%) than for US (86.9%) because of false positive results in US studies. Despite the fact that barium radiology is widely considered the method of choice in detection of internal fistulae, accuracy is not entirely satisfactory. Comparable accuracy was found for US and CT. The combination of barium and US studies, or the sole use of US in more CD patients with more severe disease, can reliably detect most internal fistulae and abscesses.
Research Interests: Computed Tomography, Ultrasound, Comparative Study, Clinical Practice, X Rays, and 14 moreProspective studies, Humans, Ultrasonography, Colonoscopy, Clinical Sciences, Radiography, Barium, Diagnostic Accuracy, X ray Computed Tomography, Prospective Study, Crohn Disease, Contrast Media, The American, and ENEMA
Seven-day proton pump inhibitor (PPI)-based triple therapies are the first-line anti-Helicobacter pylori regimens; to date, however, there is still no agreement concerning all the predictors of H. pylori cure under these regimens. The aim... more
Seven-day proton pump inhibitor (PPI)-based triple therapies are the first-line anti-Helicobacter pylori regimens; to date, however, there is still no agreement concerning all the predictors of H. pylori cure under these regimens. The aim of this prospective study was to evaluate whether patients with certain pretreatment characteristics may benefit from an extension from 1 to 2 wk of treatment with lansoprazole, amoxycillin, and clarithromycin. A total of 142 patients with H. pylori infection ascertained by means of gastric histopathology and 13C urea breath test (UBT) participated in this study. In all patients H. pylori density was determined at histology both on antral and corpus biopsies, and H. pylori culture with antibiotic susceptibility testing; IgG anti-H. pylori titers were also determined before therapy. Patients were randomized to receive 1-wk versus 2-wk of treatment with lansoprazole (30 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxycillin (1 g b.i.d.). The association between eradication and potential predictors was analyzed by means of unconditional logistic regression models and stratified according to the duration of treatment. A stepwise regression analysis was performed to identify variables discriminated between subjects, using eradication status as the dependent variable. The overall eradication rates for 1- and 2-wk treatments were 74.6% and 85.9% (intention-to-treat analysis) and 81.5% and 89.1% (per-protocol analysis), respectively (p = NS). Multivariate discriminant analysis selected as the variables independently related to eradication cigarette smoking (OR = 3.98), delta of 13C-UBT higher than 35 (OR = 9.21) and IgG anti-H. pylori titer &amp;amp;gt; or = 93 (OR = 0.24) for the whole series of subjects. Stratified analysis according to the duration of therapy selected H. pylori density as the only predictor of eradication in the group treated for 1 wk (OR = 8.11). In contrast, no significant predictors were found in the group treated for 2 wk. Patients with a high intragastric bacterial load, as detected by histology (grade 3) or 13C-UBT (delta &amp;amp;gt; 35) may benefit from an extension to 2 wk of triple therapy with lansoprazole, amoxycillin, and clarithromycin.
Research Interests: Helicobacter pylori, Logistic Regression, Prospective studies, Discriminant Analysis, Humans, and 21 moreFemale, Male, Clarithromycin, Epidemiology of Helicobacter pylori infection, Clinical Sciences, Middle Aged, Anti-Bacterial Agents, Amoxicillin, Time Factors, Prognosis, Combination drug therapy, Logistic Regression Model, Stepwise Regression, Antibiotic Susceptibility, Logistic Models, Prospective Study, Lansoprazole, H Pylori, The American, Proton Pump Inhibitor, and Proton Pump Inhibitors
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Background Lynch Syndrome (LS) correlated colorectal carcinoma (CRC) patients show a tendency towards the development of multiple and metachronous lesions and, for this reason, a surgical prophylactic treatment, as total colectomy, is... more
Background Lynch Syndrome (LS) correlated colorectal carcinoma (CRC) patients show a tendency towards the development of multiple and metachronous lesions and, for this reason, a surgical prophylactic treatment, as total colectomy, is warranted. Considering ...
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Magnetic resonance cholangiopancreatography and contrast-enhanced magnetic resonance cholangiopancreatography versus endoscopic ultrasonography in the diagnosis of extrahepatic biliary pathology | Colangiopancreatografia con risonanza magnetica e risonanza magnetica con mezzo di contrasto versus ...more
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Alteration of cardiomyocyte gap-junctions and component connexins (Cx) has been suggested to contribute to the development of atrial fibrillation (AF), including postoperative AF. We tested different possible stimuli, such as hypoxia and... more
Alteration of cardiomyocyte gap-junctions and component connexins (Cx) has been suggested to contribute to the development of atrial fibrillation (AF), including postoperative AF. We tested different possible stimuli, such as hypoxia and ischemia, influencing Cx43 and Cx40 expression and distribution in cultured atrial cells (HL-1) and reversibility of these processes after reoxygenation. Western-blot analysis and immunostaining using anti-Cx43, anti-Cx40 and anti-zonula occludens polyclonal antibodies were performed. HL-1 cells exposed to hypoxia for 24 and 48 h showed a reduction of Cx43 protein levels by 75% and 90% respectively (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). During reoxygenation following 24 h of hypoxia, Cx43 levels increased to reach the basal level within 48 h, while they remained at low level during reoxygenation following 48 h of hypoxia. Furthermore, atrial cardiomyocytes subjected to simulated ischemia (SI) were incubated in normoxic and hypoxic conditions for 3, 6, 9, 12 h. Atrial cardiomyocytes subjected to SI in addition to normoxia showed a progressive reduction of Cx43 levels beginning from 3 h. During SI and hypoxia, atrial Cx43 levels showed an initial decrease after 3 h with a subsequent rescue beginning from 6 h of exposure (p = 0.001). Hypoxia and ischemia per se downregulate Cx43 protein expression in atrial cardiomyocytes, but protein downregulation is reversible, depending on hypoxia duration and the association of the two triggers. These alterations characterize several conditions and might contribute to the generation of an arrhythmogenic substrate leading to AF onset and/or maintenance.
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Five male Sicilian children with glucose-6-phosphate dehydrogenase deficiency were studied shortly after hemolytic crisis in order to evaluate the immediate effects of massive hemolysis on fetal Hb (HbF) levels and the number of... more
Five male Sicilian children with glucose-6-phosphate dehydrogenase deficiency were studied shortly after hemolytic crisis in order to evaluate the immediate effects of massive hemolysis on fetal Hb (HbF) levels and the number of circulating F cells. Hematological values seen 4 months after the children recovered from the crisis were considered representative of the patients&amp;amp;#39; steady state. All patients had an increase in HbF levels (2.26 +/- 0.24%) and F cell number (29 +/- 4.79%) in the acute phase and their HbF values and F cells returned to normal range at control. Globin synthesis was balanced in the peripheral blood and bone marrow and there was a small peak of gamma chains. Globin chain electrophoresis showed that both G gamma and A gamma genes were active in all patients. These results confirm that hemolytic stress produces increased F cell release in peripheral blood. Such release is rapid enough (less than 72 h) to be consistent with the hypothesis of an induction of HbF synthesis in late erythroid precursors.
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Research Interests: Engineering, Physics, Chemistry, Biology, Medicine, and 17 moreMultidisciplinary, Colorectal cancer, Cell Differentiation, Humans, Intestinal Mucosa, Female, Male, Cell Polarity, PLoS one, Aged, Caco-2 cells, Adult, Colon, Plasma Membrane, Protein Transport, Insulin Receptor Substrate, and Colorectal Neoplasms
Ifosfamide is an alkylating agent that is widely used in the treatment of various neoplasms, such as sarcomas, lymphomas, pediatric malignancies, germ cell tumors, lung, breast and ovarian cancer. The clinical toxicity of ifosfamide... more
Ifosfamide is an alkylating agent that is widely used in the treatment of various neoplasms, such as sarcomas, lymphomas, pediatric malignancies, germ cell tumors, lung, breast and ovarian cancer. The clinical toxicity of ifosfamide depends on the dose and administration schedules. The pharmacologic features of this drug enable its combination with other antiblastic agents, such as vinorelbine, gemcitabine, paclitaxel and docetaxel. Moreover, the pharmacologic profile of ifosfamide allows the use of this antiblastic drug in patients who have previously failed many other treatments, and a large percentage of responses has already been obtained. There is some concern about the optimal scheduling of the drug with other novel chemotherapeutics. Clinical trials that include pharmacokinetic and pharmacodynamic studies may be the most efficient way to optimize the therapeutic efficacy of ifosfamide and define the dosing and scheduling.
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Research Interests: Oncology, Quality of life, Italy, Humans, Medical Oncology, and 7 moreFemale, Male, Physicians, Aged, Middle Aged, Questionnaires, and Adult
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Research Interests: Breast Cancer, Transcription Factors, Gene expression, Molecular Mechanics, Estrogen Receptor, and 18 moreTranscription, Humans, Female, HIstone Deacetylase, Oncogene, DNA methylation, Proteins, Enzyme, Chromatin, Clinical Sciences, Histones, Acetylation, Breast carcinoma, DNA binding proteins, Breast Cancer Cells, Histone deacetylases, Estrogen receptor-beta, and Estrogen receptor alpha
We studied the correlation between fecal levels of short-chain fatty acids (SCFA), bile acids (BA), and colonic mucosal proliferation in humans on a free diet. Subjects [n = 43: 27 men and 16 women; 61 +/- 7 and 59 +/- 6 (SE) yr old,... more
We studied the correlation between fecal levels of short-chain fatty acids (SCFA), bile acids (BA), and colonic mucosal proliferation in humans on a free diet. Subjects [n = 43: 27 men and 16 women; 61 +/- 7 and 59 +/- 6 (SE) yr old, respectively] were outpatients who previously underwent resection of at least two sporadic colon polyps. Mucosal proliferation was determined by [3H]thymidine incorporation in vitro in three colorectal biopsies obtained without cathartics and was expressed as labeling index (LI). BA were analyzed in feces by mass spectrometry and SCFA by gas chromatography. We found that increasing levels of BA in feces did not correlate with higher LI. On the contrary, higher levels of SCFA were significantly associated with lower LI in the colonic mucosa (P for trend = 0.02). In conclusion, in humans on a free diet, intestinal proliferation seems to be regulated by the levels of SCFA in feces and not by BA. Because a lower intestinal proliferation is associated with a decreased colon cancer risk, treatments or diets that increase colonic levels of SCFA might be beneficial for colonic mucosa.
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The proliferative activity was evaluated in colorectal biopsies of 39 healthy subjects living in two distinct geographical areas, Trieste in northern and Florence in central Italy. Subjects living in Trieste had a significantly higher... more
The proliferative activity was evaluated in colorectal biopsies of 39 healthy subjects living in two distinct geographical areas, Trieste in northern and Florence in central Italy. Subjects living in Trieste had a significantly higher mitotic activity compared with subjects living in Florence (mitoses/cells counted x 100 were 0.17 +/- 0.04 in Trieste and 0.089 +/- 0.02 in Florence). The results of a dietary questionnaire also showed that subjects in Trieste consumed significantly fewer starches, fibers, nitrites, and proteins. However, no correlation was evident between the consumption of these nutrients and intestinal proliferation.
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Migraine is a complex and often disabling brain disorder that affects about 15 % of the population. The diagnosis of migraine is based on clinical features as proposed by the International Headache Society criteria but they are somewhat... more
Migraine is a complex and often disabling brain disorder that affects about 15 % of the population. The diagnosis of migraine is based on clinical features as proposed by the International Headache Society criteria but they are somewhat subjective and arbitrary. Functional neuroimaging of patients with migraine has been recently employed to study the underlying pathophysiology of headache. These studies have suggested that migraine involves functional and structural plasticity of both central and peripheral nervous system. Insights into the fundamental physiology of migraine have been limited by the lack of methods available to detect the pathophysiological background of critical moment of migraine attack onset that is greatly different from the onset of pain or pain phase of a migraine attack. In order to overcome methodological caveats in detecting &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;migraine origin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; or a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;migraine generator&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, functional brain imaging has been lately dominated by experimental acute-pain research. Along this research line functional imaging using experimental pain stimulation have greatly improved our knowledge about physiological or dysfunctional neuronal activity pattern in patients with migraine, but at the same time, it is important to emphasize that experimental pain is different from spontaneous migraine pain.