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1.  Adherence in HIV-positive patients treated with single-tablet regimens and multi-pill regimens: findings from the COMPACT study 
The use of Combination AntiRetroviral Therapy (cART) has decreased the morbidity and mortality of patients infected with HIV. However, adherence to cART remains crucial to prevent virological failure and disease progression. The aim of this study was to assess adherence to treatment among patients treated with Single Tablet Regimen (STR) or with multi-pill regimens based on Protease Inhibitors (PI), Non-Nucleoside Reverse-Transcriptase Inhibitors (NNRTI), or raltegravir (RAL). An observational retrospective cohort analysis based on administrative and clinical databases was conducted at the National Institute for Infectious Diseases (Rome, Italy). HIV-positive patients treated with a cART between Jan 1st, 2008–Dec 31st, 2010 were included. Patients were followed-up for one year since the first prescription during the inclusion period or up to death or switch of at least one drug of the regimen. Adherence and selective non-adherence (days without backbone or 3rd drug) were calculated using pharmacy refill compliance [1]. cART regimens were classified based on number of daily pills (STR vs multi-pill regimen) and on type of third drug. Viral Load (VL) and CD4 cell counts at the end of the follow-up were evaluated. A total of 1,604 patients were analyzed, 70.0% male, age 45.0±8.7, 14.3% newly treated. Patients on STR were 159 (9.9%), PI 878 (54.7%), NNRTI 523 (32.6%), RAL 44 (2.7%). Presence of at least one AIDS-defining conditions (according to Centers for Disease Control classification) was 30% in the STR group, 34% PI, 26% NNRTI, 34% RAL (p=n.s.). Adherence was 80.4±14.7% for STR, 71.8±21.8% PI, 77.1±20.3% NNRTI, 74.0±22.4% RAL. Selective non-adherence was 5.5% (18 days) PI, 2.8% (8 days) NNRTI, 12.5% (43 days) RAL (Figure 1). At the end of the follow-up, VL/CD4 values were available among 709 patients (44%); CD4 count >500 cell/mm3 was observed among 61% of patients on STR, 44% PI, 48% NNRTI, 42% RAL and VL < 50 copies/ml was observed among 96% of patients on STR, 78% PI, 88% NNRTI, 87% RAL. Interruptions in cART refill remain a relevant problem across all cART regimens. Patients on STR displayed a higher adherence rate compared to multi-pill regimes (PI, NNRTI, and RAL), primarily due to lack of selective non-adherence. Patients on STR experienced also higher rates of VL < 50 and CD4 > 500. The use of an STR regimen appears an effective therapeutic option to avoid selective non-adherence and, consequently, to prevent virological failure and disease progression.Figure 1Non-adherence to cART regimens.
PMCID: PMC3512502
2.  Risk of Kaposi's sarcoma and of other cancers in Italian renal transplant patients 
British Journal of Cancer  2005;92(3):572-575.
A follow-up study of 1844 renal transplant patients in Italy showed a 113-fold increased risk for Kaposi's sarcoma. Kaposi's sarcoma risk was higher in persons born in southern than in northern Italy. Significant increases were also observed for cancers of the lip, liver, kidney and for non-Hodgkin's lymphoma.
PMCID: PMC2362080  PMID: 15668710
renal transplant; cancer risk; Kaposi's sarcoma; liver cancer; Italy
3.  A high vascular count and overexpression of vascular endothelial growth factor are associated with unfavourable prognosis in operated small cell lung carcinoma 
British Journal of Cancer  2002;86(4):558-563.
It has been widely demonstrated that neo-angiogenesis and its mediators (i.e. vascular endothelial growth factor), represent useful indicators of poor prognosis in non small cell lung carcinoma. In order to verify whether neovascularization and vascular endothelial growth factor may be considered useful markers of clinical outcome also in the small cell lung cancer subgroup, we retrospectively investigated a series of 75 patients with small cell lung carcinoma treated by surgery between 1980 and 1990. Immunohistochemically-detected microvessels and vascular endothelial growth factor expressing cells were significantly associated with poor prognosis, as well as with nodal status and pathological stage. In fact, patients whose tumours had vascular count and vascular endothelial growth factor expression higher than median value of the entire series (59 vessels per 0.74 mm2 and 50% of positive cells, respectively), showed a shorter overall and disease-free survival (P=0.001, P=0.001; P=0.008, P=0.03). Moreover, the presence of hilar and/or mediastinal nodal metastasis and advanced stage significantly affected overall and disease-free interval (P=0.00009, P=0.00001; P=0.0001, P=0.00001). At multivariate analysis, only vascular endothelial growth factor expression retained its influence on overall survival (P=0.001), suggesting that angiogenic phenomenon may have an important role in the clinical behaviour of this lung cancer subgroup.
British Journal of Cancer (2002) 86, 558–563. DOI: 10.1038/sj/bjc/6600130
© 2002 Cancer Research UK
PMCID: PMC2375289  PMID: 11870537
angiogenesis; VEGF; small cell lung cancer
4.  Tumour necrosis factor- α and transforming growth factor- β are significantly associated with better prognosis in non-small cell lung carcinoma: putative relation with BCL -2-mediated neovascularization 
British Journal of Cancer  2000;83(4):480-486.
Recent in vivo and in vitro studies have demonstrated a wide spectrum of biologic activities of cytokines in the pathogenesis and progression of malignancy. Tumour necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β) have emerged as two of the many host-derived mediators that seem to interfere with both antiproliferative and tumorigenic effects in malignant tumours including lung cancer. However, their association with tumour prognosis or prognostic factors has not yet been completely clarified. In this study, we assessed TNF-α and TGF-β mRNA expression by RT-PCR technique in 61 NSCLC samples, demonstrating the presence of TNF-α and TGF-β mRNA in 55.74% and 45.9% of cases, respectively. We also evaluated the expression of the two distinct transmembrane TNF receptors. TNFR-I and TNFR-II, with a PCR-positive signal in 70.49% and 65.57% of cases, respectively. In 49 of the 61 cases, we evaluated the prognostic impact of the two growth-inhibiting factors using the Kaplan–Meier analysis. In the univariate analysis patients without nodal metastatic involvement (P = 0.02), less advanced tumour stage (P = 0.02) or TNF-α and TGF-β positive cancers (P = 0.01 and P = 0.03) showed a favourable prognosis in terms of overall survival. Since our previous studies demonstrated a significant association between NSCLC behaviour, neoangiogenesis and bcl -2 expression, we investigated the putative relation between TNF-α and TGF-β on the one hand, and vascular count (as a measure of tumour angiogenesis) and bcl -2 protein expression, on the other hand. Our results showed a significant direct association between TNF-α and bcl -2 (P = 0.05) and an inverse association between TNF-α and microvessel count (P = 0.03). Moreover, as previously demonstrated, we observed a significant inverse correlation between bcl -2 protein expression and vascular count (P = 0.05), suggesting that the favourable effect of TNF-α on clinical outcome may be related to a bcl -2-mediated low neovascular development. © 2000 Cancer Research Campaign
PMCID: PMC2374649  PMID: 10945495
NSCLC; tumour necrosis factor alpha; transforming growth factor beta; angiogenesis; prognosis
5.  Expression of vascular endothelial growth factor mRNA in non-small-cell lung carcinomas 
British Journal of Cancer  1999;79(2):363-369.
The vascular endothelial growth factor (VEGF) has been shown to be strictly related to vascular permeability and endothelial cell growth under physiological and pathological conditions. In tumour development and progression, VEGF plays a pivotal role in the development of the tumoral vascular network, and useful information in the progression of human cancer can be obtained by analysing the vascular endothelial growth factor expression of the tumours. In this study, we investigated the vascular endothelial growth factor transcript expression in non-small-cell lung carcinomas to evaluate the significance of this factor in a group of cancers in which the vascular pattern has been shown to significantly affect progression. Surgical samples of 42 patients with NSCLC were studied using reverse transcription polymerase chain reaction (PCR) analysis and in situ hybridization. Thirty-three out of 42 cases (78.6%) showed VEGF transcript expression predominantly as transcripts for the secretory forms of VEGF (isoforms 121 and 165). In situ hybridization, performed on 24 out of 42 samples, showed that the VEGF transcript expression was in several cases present in the cytoplasm both of neoplastic and normal cells, even if the VEGF mRNA was less expressed in the corresponding non-tumoral part. The VEGF 121 expression was associated with hilar and/or mediastinal nodal involvement (P = 0.02), and, taken together, the VEGF isoforms were shown to significantly influence overall (P = 0.02) and disease-free survival (P = 0.03). As a regulator of tumour angiogenesis, VEGF may represent a useful indicator of progression and poor prognosis in non-small-cell lung carcinomas. © 1999 Cancer Research Campaign
PMCID: PMC2362204  PMID: 9888482
vascular endothelial growth factor; non-small-cell lung cancer; reverse transcription polymerase chain reaction; prognosis
6.  Genetic analysis of lung tumours of non-smoking subjects: p53 gene mutations are constantly associated with loss of heterozygosity at the FHIT locus. 
British Journal of Cancer  1998;78(1):73-78.
Lung cancer is strictly associated with tobacco smoking. Tumours developed in non-smoking subjects account for less than 10% of all lung cancers and show peculiar histopathological features, being prevalently adenocarcinomas. A number of genetic data suggest that their biological behaviour may be different from that of lung tumours caused by smoking, however the number of cases investigated to date is too low to draw definitive conclusions. We have examined the status of p53 and K-ras genes and the presence of loss of heterozygosity (LOH) at the FHIT locus in a series of 35 lung adenocarcinomas that developed in subjects who had never smoked. Results were compared with those obtained in a series of 35 lung adenocarcinomas from heavy-smoking subjects. In the group of non-smoking subjects p53 mutations and LOH at the FHIT locus were present in seven (20%) cases, and the two alterations were constantly associated (P < 0.0001), whereas they were not related in the series of carcinomas caused by smoking. In tumours developed in heavy-smoking subjects, the frequency of LOH at the FHIT locus was significantly higher (P = 0.006) than in tumours from non-smoking subjects. The frequency of p53 mutations in adenocarcinomas caused by smoking was not different from that seen in non-smoking subjects. However, in the group of smoking subjects we observed mostly G:C --> T:A transversions, whereas frameshift mutations and G:C --> A:T transitions were more frequently found in tumours from non-smoking subjects. No point mutations of the K-ras gene at codon 12 were seen in subjects who had never smoked, whereas they were present (mostly G:C --> T:A transversions) in 34% of tumours caused by smoking (P = 0.002). Our data suggest that lung adenocarcinomas developed in subjects who had never smoked represent a distinct biological entity involving a co-alteration of the p53 gene and the FHIT locus in 20% of cases.
PMCID: PMC2062949  PMID: 9662254
7.  Neoangiogenesis and p53 protein in lung cancer: their prognostic role and their relation with vascular endothelial growth factor (VEGF) expression. 
British Journal of Cancer  1997;75(9):1295-1301.
Following up-regulation of an angiogenesis inhibitor by the wild-type p53 protein proven recently, we have analysed on the one hand the prognostic impact of microvessel count (MC) and p53 protein overexpression in non-small-cell lung carcinoma (NSCLC) progression and, on the other hand, the inter-relation between the microvascular pattern and the p53 protein expression. Moreover, we assessed the expression of vascular endothelial growth factor (VEGF), one of the pivotal mediators of tumour angiogenesis, in order to investigate its relation to p53 protein expression and MC. Tumours from 73 patients resected for NSCLC between March 1991 and April 1992 (median follow-up 47 months, range 32-51 months) were analysed using an immunohistochemical method. In univariate analysis, MC and p53 accumulation were shown to affect metastatic nodal involvement, recurrence and death significantly. Multiple logistic regression analysis showed an important prognostic influence of MC and nodal status on overall (P = 0.0009; P = 0.01) and disease-free survival (P = 0.0001; P = 0.03). Interestingly, a strong statistical association was observed between p53 nuclear accumulation and MC (P = 0.0003). The same inter-relationship was found in non-squamous histotype (P = 0.002). When we analysed the concomitant influence of MC and p53 expression on overall survival, we were able to confirm a real predominant role of MC in comparison with p53. With regard to VEGF expression, p53-negative and lowly vascularized tumours showed a mean VEGF expression significantly lower than p53-positive and highly vascularized cancers (P = 0.02). These results underline the prognostic impact of MC and p53 protein accumulation in NSCLC and their reciprocal inter-relationship, supporting the hypothesis of a wild-type p53 regulation on the angiogenetic process through a VEGF up-regulation.
PMCID: PMC2228220  PMID: 9155049
8.  Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer. 
British Journal of Cancer  1995;71(5):1003-1007.
Non-small-cell lung cancer (NSCLC) prognosis is strictly related to well-established clinicopathological parameters which have unfortunately become insufficient in the prognostic evaluation of this type of cancer. As p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancies, we investigated the Bcl-2 and p53 protein expression in 91 and 101 cases of NSCLC respectively. The expression was then compared with established indicators of prognosis and biological behaviour of the tumours. No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was significantly lower in patients who developed metastasis during follow-up or died of metastatic disease (P = 0.006 and P = 0.01 respectively). Moreover, survival probability was higher in patients who expressed the Bcl-2 protein (P = 0.0002). In contrast with this, p53 protein accumulation was observed in tumours with metastatic nodal involvement (P = 0.02) or in patients who developed metastasis during follow-up (P = 0.01), although no correlation was found between p53 expression and overall survival. An inverse relationship was also found between Bcl-2 and the anti-oncogene protein product p53 (P = 0.01). Thus, a high proportion of NSCLCs express p53 and Bcl-2 proteins and their expression may have prognostic importance.
PMCID: PMC2033793  PMID: 7734290
9.  Surgical treatment of primary lung cancer and solitary brain metastasis. 
Thorax  1985;40(3):191-193.
Twenty patients with carcinoma of the lung and a brain metastasis have undergone combined lung and brain surgery, which was synchronous in five. There were no operative deaths. Survival from the first surgical intervention was less than one year (3-10 months) in four patients (20%), one to two years in four (20%) and more than two years (26-66 months) in five patients (25%). Seven patients (35%) are alive and well after an average period of three years and three months (15-66 months). Actuarial survival at five years is 33.6%. All patients had severe neurological symptoms and 18 (90%) had a complete remission. Our experience and data reported in the literature point to the effectiveness of combined lung and brain surgery in prolonging symptom free survival in patients with lung cancer and solitary brain metastasis.
PMCID: PMC460026  PMID: 3983887

Results 1-9 (9)