70 research outputs found
Targeted therapies for Malignant Mesothelioma
No full textMalignant mesothelioma (MM) is an aggressive neoplasia arising from mesothelial cells that line serous cavities, such as pleura, peritoneum, pericardium, and vaginal tunic. It is defined as an occupational disease because it is related to asbestos exposure. It mainly affects people between 50 and 70 years of age, with a male to female mortality ratio of 4:1. Despite traditional multidisciplinary treatment, involving the combination of chemotherapy, radiotherapy and surgery, prognosis remains poor. This is partly due to the delay of the diagnosis and partly due to the inadequacy of therapeutic approaches. The aim of this project is to find new therapeutic strategies for the treatment of MM based on a molecular targeted approach.
In this study the in vitro and in vivo anticancer effects of Bortezomib (Bor), the first selective and reversible proteasome inhibitor, on MM have been investigated. Bor was able to inhibit cell growth in a dose- and time-dependent manner; to induce apoptosis in treated cell lines, both human (H-Meso-1, MM-F1 and MM-B1) and murine (#40a); to modulate the expression of several molecules deregulated in MM, such as EGFR, ErbB2 and AKT; to induce Unfolded Protein Response, altering the expression of Grp78, CHOP and BiP. In vivo studies on C57BL/6 murine MM model have shown that Bor inhibited tumor growth and increased mice overall survival. Moreover, Bor treatment was able to modulate tumor immune microenvironment [1].
The ErbB receptor family is often overexpressed in MM patients and the use of EGFR-targeted drugs can inhibit MM cell proliferation. It is described that the use of a specific unitarget drugs can induce drug-resistance leading to the activation of different deregulated signaling pathways, such as those mediated by ErbB family receptor, Hedgehog, Axl, Wnt [2]. Recent studies in our laboratory, investigated the in vitro and in vivo effects of a specific inhibitor of ErbB family receptor, Afatinib (AFA), in combination with a multitarget molecule, Curcumin (CUR). CUR was able to enhance AFA effects increasing the AFA-induced reduction of the proliferation rate and pro-apoptotic effects in vitro. Indeed, in vivo AFA-antitumor activity was enhanced by its combination with CUR significantly increasing mice overall survival [3].
In another study from our laboratory the effects of inhibitors of Hh- (GANT-61) and ErbB receptors (AFA)-mediated signaling pathways, involved in neoplastic transformation and progression, were evaluated. The combined treatment with two inhibitors was more effective than the single treatments in reducing MM growth in vitro and in vivo, overcame the occurrence of drug resistance.
Based on these results, we are currently studying whether combined treatment using three different molecular targeted drugs, used at low doses, is more effective than single and dual treatments in inhibiting tumor growth in MM. Specifically, we are testing the combination of AFA, with Y15, a FAK inhibitor, and TP-0903, an Axl inhibitor.
Our preliminary data showed an increase of cell proliferation inhibition, with a proportional increase in cell death, in all cell lines treated with the triple combination compared to single and dual treatments in a time-dependent manner. Moreover, the use of 3D cultures has made possible to study the antitumor effects of these three inhibitors on systems that are more complex and more representative of in vivo tumor models. Spheroids treated with AFA, Y15 or TP-0903, used alone or in double combination, showed a significant inhibition of growth compared to control spheroids, and the triple combination significantly decreases spheroid growth compared to control, single or double treated spheroids. Finally, the triple combination reduced cell viability in treated spheroids compared to control ones.
In conclusion, targeted therapy offers significant promise in achieving better treatment outcomes with fewer side effects than conventional therapies. This study could be helpful in developing new personalized therapies that are more effective for MM patient
Clinical course of ulcerative colitis
No full text. Dig Liver Dis. 2008 Jul;40 Suppl 2:S247-52.
Clinical course of ulcerative colitis.
Cottone M, Scimeca D, Mocciaro F, Civitavecchia G, Perricone G, Orlando A.
Department of Medicine, Pneumology and Nutrition Clinic, V. Cervello Hospital,
University of Palermo, Palermo, Italy.
AIM: To provide a review of studies on prognosis in ulcerative colitis by
reviewing the relevant population-based cohort studies. On the basis of incidence
and population studies, ulcerative colitis has a favourable clinical course, with
good quality of life, a chronic course characterized by at least one relapse, and
a surgery rate of 30% after 10 years from diagnosis. Patients affected by severe
ulcerative colitis have a higher risk of colectomy, and some clinical variables
may predict the disease's clinical course. Most patients respond to steroids and
only a low percentage become dependent, or non-responders to steroids. Patients
who have a long-lasting ulcerative colitis (>10 years) or are affected by an
extensive disease have an increased risk of developing colorectal cancer, while
those treated with immunosuppressants for long period of time may have an
increased risk of developing lymphomas. Data on mortality in ulcerative colitis
patients are not homogeneous, but if a real risk exists it is in patients with
extensive or severe disease. The evidence that patients with severe ulcerative
colitis are often non-smokers may explain why in one study the mortality rate was
lower
Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in post-operative Crohn's disease
No full textMeta-analysis of the placebo rates of clinical relapse and severe endoscopic
recurrence in postoperative Crohn's disease.
Renna S, Cammà C, Modesto I, Cabibbo G, Scimeca D, Civitavecchia G, Mocciaro F,
Orlando A, Enea M, Cottone M.
Dipartimento di Medicina, Pneumologia e Fisiologia della Nutrizione Umana,
Università di Palermo, Palermo, Italy.
BACKGROUNDS & AIMS: The benefit of therapy for prevention of postoperative
recurrence of Crohn's disease (CD) is limited. Clinical relapse and severe
endoscopic recurrence are the main outcomes in the evaluation of trials on
prevention of recurrence. The aim of this meta-analysis was to focus on knowledge
of the placebo rates of relapse and recurrence in postoperative CD and to
identify factors influencing these rates.
METHODS: We performed a meta-analysis of placebo-controlled, randomized clinical
trials, evaluating therapies for postoperative maintenance of CD identified on
MEDLINE from 1990 to 2006. Primary outcomes were clinical relapse and severe
endoscopic recurrence.
RESULTS: The pooled estimate of the placebo relapse rate was 23.7% (95%
confidence interval [CI], 13-35; range 0-78). There was a statistically
significant heterogeneity among studies (P < .0001). Heterogeneity in clinical
relapse was present even if the trials were stratified according to the time of
outcome. The pooled estimate of the severe endoscopic recurrence rate was 50.2%
(95% CI, 28-73; range, 30-79). There was significant heterogeneity among the
studies (P = .00038). This heterogeneity was less apparent in studies carried out
within 12 months. The logistic analysis identified only duration of follow-up as
a variable associated with different placebo relapse rates. No variable was
identified as a predictor of a placebo endoscopic recurrence rate.
CONCLUSIONS: There is significant heterogeneity among placebo rates in
postoperative CD. No single design variable was identified that explained the
heterogeneity in placebo outcomes for clinical or endoscopic recurrence
Aripiprazole plus Topiramate in Opioid-Dependent Patients with Schizoaffective Disorder: An 8-Week, Open-Label, Uncontrolled, Preliminary Study
No full text.Background: The aims of this study were to evaluate a combination of aripiprazole and topiramate in the treatment of opioid-dependent patients with schizoaffective disorder undergoing methadone maintenance therapy (MMT) and, further, to taper off patients from methadone treatment. Methods: Twenty patients who met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for opioid dependence and schizoaffective disorder receiving MMT (80mg/day) were given aripiprazole (10mg/day) plus topiramate (up to 200mg/day) for 8 weeks. A methadone dose reduction of 3mg/day until suspension at week 4 was established. Results: Aripiprazole plus topiramate was effective in reducing clinical symptoms, and a rapid tapering off of MMT was achieved. Conclusions: Combining aripiprazole and topiramate may be effective in patients with a dual diagnosis of opioid dependency and schizoaffective disorder
THE ROLE OF CARD15 MUTATIONS AND SMOKING IN THE COURSE OF DISEASE IN A MEDITERRANEAN AREA
No full text. Am J Gastroenterol. 2008 Mar;103(3):649-55.
The role of CARD15 mutations and smoking in the course of Crohn's disease in a
Mediterranean area.
Renda MC, Orlando A, Civitavecchia G, Criscuoli V, Maggio A, Mocciaro F, Rossi F,
Scimeca D, Modesto I, Oliva L, Cottone M.
Ematologia II Ospedale V. Cervello, Palermo, Italy.
AIM: To evaluate the role of CARD15 mutations and smoking in the main events of
Crohn's disease (CD).
PATIENTS AND METHODS: A total of 182 patients with CD were included in a
prospective study in order to evaluate the role of CARD15 mutations and smoking
in the main outcomes of disease course: first operation and surgical recurrence.
The following variables were evaluated in a univariable and multivariable
analysis: age, sex, site of disease, pattern, smoking habit, extraintestinal
manifestations, duration of disease, and CARD15 mutation. The Kaplan-Meier method
for survival curves and Cox model for multivariable analysis were, respectively,
used.
RESULTS: A total of 110 patients were operated on and 32 were reoperated on. The
7-yr cumulative free rate of surgery was 42% (95% CI 34-51%). At multivariate
analysis only stricturing and penetrating pattern were predictors of surgery (HR
1.7, 95% CI 1-2.8; HR 3.2, CI 1.8-5.5, respectively). The 7-yr cumulative free
rate of reoperation was 75% (95% CI 0.52-0.88). At multivariable analysis in the
model with any CARD15 mutation, only smoking habit at diagnosis (HR 3.6, 95% CI
1.4-9.1) was predictive of surgical recurrence. When single mutations were
considered in the model smoking (HR 4.2, 95% CI 1.8-10.1) and L1007fs mutation
(HR 2.9, 95% CI 1.1-7.3) were predictive of reoperation.
CONCLUSIONS: In CD, smoking predicts recurrence after surgery. The role of CARD15
mutations in the clinical course of CD remains undefined
Unraveling Exercise Addiction: The Role of Narcissism and Self-Esteem
No full textThe aim of this study was to assess the risk of exercise addiction (EA) in fitness clubs and to identify possible factors in the development of the disorder. The Exercise Addiction Inventory (EAI), the Narcissistic Personality Inventory (NPI), and the Coopersmith Self-Esteem Inventory (SEI) were administered to a sample of 150 consecutive gym attenders recruited in fitness centers. Based on EAI total score, high EA risk group (HEA n = 51) and a low EA risk group (LEA n = 69) were identified. HEA reported significantly higher total score (mean = 20.2 versus 14.6) on the NPI scale and lower total score (mean = 32.2 versus 36.4) on the SEI scale than LEA. A stepwise regression analysis indicated that only narcissism and self-esteem total scores (F=5.66; df=2; P=0.006)weregoodpredictorsofdaysperweekexercise.Thepresentstudyconfirmsthedirectandcombined role of both labile self-esteem and high narcissism in the development of exercise addiction as predictive factors towards the risk of addiction. Multidisciplinary trained health care providers (physiatrists, psychologists, and psychiatrists) should carefully identify potential overexercise conditions in order to prevent the potential risk of exercise addiction
Infliximab in moderate to severe sateroid dipendent or refractory severe ulcerative colitis:short term results of 21 case treated
No full textThe relationship between personality and sexual motivation: an investigation based on Cloninger’s model in nonclinical Italian subjects
No full textThe aim of this study was to investigate the relationship between personality and sexual motiva- tion according to Cloninger’s psychobiological model of the personality. Methods. Three hundred and ten volunteers re- cruited among the students of the University of Messina, Italy, participated in the study. All subjects underwent a psychome- tric examination with the following instruments: Temperament and Character Inventory (TCI) and Sex and the Average Woman (or Man; SAWM). Results. The best negative predictor of Sexual Excitement and Satisfaction was the tempera- mental dimension Harm Avoidance; as it regards character dimensions, Cooperativeness was the best negative predictor of Sexual Excitement, while Self-Directedness was the best positive predictor of Sexual Satisfaction. Conclusions. Overall, in- hibitory aspects of the personality have deeper effects on sexual motivation than excitatory ones. The results of this research suggest the importance of studying the relationship between personality and sexual behavior. An integrative psychobiologi- cal approach to the study of sexual excitement and satisfaction may give a fundamental contribution to the assessment and psychological treatment of predisposing personality factors (like avoidant tendencies) involved in the development and per- sistence of sexual dysfunction
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