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author:("príncipe, M")
2.  Cellular senescence induced by aberrant MAD2 levels impacts on paclitaxel responsiveness in vitro 
British Journal of Cancer  2009;101(11):1900-1908.
The mitotic arrest deficiency protein 2 (MAD2) is a key component of the mitotic spindle assembly checkpoint, monitoring accurate chromosomal alignment at the metaphase plate before mitosis. MAD2 also has a function in cellular senescence and in a cell's response to microtubule inhibitory (MI) chemotherapy exemplified by paclitaxel.
Using an siRNA approach, the impact of MAD2 down-regulation on cellular senescence and paclitaxel responsiveness was investigated. The endpoints of senescence, cell viability, migration, cytokine expression, cell cycle analysis and anaphase bridge scoring were carried out using standard approaches.
We show that MAD2 down-regulation induces premature senescence in the MCF7 breast epithelial cancer cell line. These MAD2-depleted (MAD2↓) cells are also significantly replicative incompetent but retain viability. Moreover, they show significantly higher levels of anaphase bridges and polyploidy compared to controls. In addition, these cells secrete higher levels of IL-6 and IL-8 representing key components of the senescence-associated secretory phenotype (SASP) with the ability to impact on neighbouring cells. In support of this, MAD2↓ cells show enhanced migratory ability. At 72 h after paclitaxel, MAD2↓ cells show a significant further induction of senescence compared with paclitaxel naive controls. In addition, there are significantly more viable cells in the MAD2↓ MCF7 cell line after paclitaxel reflecting the observed increase in senescence.
Considering that paclitaxel targets actively dividing cells, these senescent cells will evade cytotoxic kill. In conclusion, compromised MAD2 levels induce a population of senescent cells resistant to paclitaxel.
PMCID: PMC2788249  PMID: 19935801
mitotic assembly deficient protein 2 (MAD2); cellular senescence; paclitaxel resistance; breast cancer
4.  Removable Partial Prosthesis (RPP) with acrylic resin flange for the mandibular guidance therapy 
Patients undergoing hemimandibulectomy suffer from mandibular deviation.
The purpose of this article is to describe a new therapeutic possibility for the prosthetic management of these patients using only one device both for physiotherapy and eating.
A 56-year-old man’s pre-existing mandibular removable partial prosthesis was modified to use as a partial prosthesis as a device to correct mandibular deviation. In fact, two precision attachments patrix were inserted into buccal surface of partial prosthesis base and corresponding matrix were inserted into a transparent acrylic resin guide-flange.
In this way the patient can use only one prosthesis both for physiotherapy and eating simply inserting and removing the guide flange. The transparent resin employ is important for the day by day use.
This technique permits to use only one device both for mechanical correction of mandibular deviation and masticatory function while literature shows that two different devices are usually used in patients with mandibular deviation to satisfy both these functions.
PMCID: PMC3454023  PMID: 23139463
Hemimandibulectomy; Mandibular deviation; Guide flange prosthesis
5.  Expression and heterodimer‐binding activity of Ku70 and Ku80 in human non‐melanoma skin cancer 
Journal of Clinical Pathology  2006;59(11):1181-1185.
Experimental data suggest that exposure to ultraviolet radiation may indirectly induce DNA double‐strand breaks.
To investigate the contribution of the non‐homologous end‐joining repair pathway in basal and squamous cell carcinomas.
Levels of Ku70 and Ku80 proteins were determined by immunohistochemical analysis and Ku70–Ku80 heterodimer‐binding activity by electrophoretic mobility shift assay. Matched pathological normal margins and skin from healthy people were used as controls.
A significant increase in Ku70 and Ku80 protein levels was found for both tumour types as compared with normal skin (p<0.001). Squamous cell carcinoma showed increased immunostaining as compared with basal cell tumours (p<0.02). A direct correlation was found between Ku70 and Ku80 protein levels and expression of the proliferation markers Ki‐67/MIB‐1 (p<0.02 and p<0.002, respectively) in basal cell carcinoma. DNA binding activity was increased in basal cell carcinoma samples as compared with matched skin histopathologically negative for cancer (p<0.006). In squamous cell carcinomas, however, the difference was significant only with normal skin (p<0.02) and not with matched pathologically normal margins.
Overall, an up regulation of the Ku70 and Ku80 protein levels seems to correlate only with tumour proliferation rate. As non‐homologous end joining is an error‐prone mechanism, its up regulation may ultimately increase genomic instability, contributing to tumour progression.
PMCID: PMC1860517  PMID: 16497868
6.  Prevalence of headache in an elderly population: attack frequency, disability, and use of medication 
OBJECTIVES—To assess the 1 year prevalence of tension-type headache (TTH), migraine headache (MH), and chronic daily headache (CDH), as well as of headache in general in a rural elderly population.
METHODS—A door to door two phase survey was carried out on all elderly (⩾65 years) residents in three villages in central Italy. Participants completed a standardised headache questionnaire and underwent a clinical evaluation by a neurologist. Headache diagnosis was made according to the classification of the International Headache Society, with minor modifications for the classification of patients with MH with⩾15 attacks/month.
RESULTS—Eight hundred and thirty three (72.6%) of the 1147 eligible persons completed the study protocol. One year prevalence rates were respectively 44.5% for TTH, 11.0% for MH, 2.2% for symptomatic headaches, and 0.7% for the remaining types of headache. The prevalence of headache in general was 51.0% because 62 residents had both TTH and MH attacks. Prevalence rates of patients with headache were higher in women than men (62.1% and 36.6% respectively) and decreased steadily with age for the 65-74, 75-84, and 85-96 age groups (56.7%, 45.2% and 26.1% respectively). Prevalence rates were 20.4% for patients with moderate to severe attacks, 18.0% for those with ⩾1 attacks a month, and 4.4% for those with CDH. Of the 425 with headache 52 (12.2%) had not taken any drugs for their attacks in the previous year, 195 (45.9%) had taken them regularly, and 178 (41.9%) had taken them only when the headache pain interfered with activities that could not be postponed. Medication overuse was reported by 37.8% of patients with CDH with higher proportions for transformed migraine than for patients with chronic TTH (69.2% and 23.8% respectively, p=0.009)
CONCLUSIONS—A consistent proportion of elderly people have primary headaches and consultation with a specialist is particularly recommended for patients with moderate or severe attacks, or with CDH.

PMCID: PMC1737286  PMID: 11181862
7.  Prevalence of dementia in an elderly rural population: effects of age, sex, and education. 
OBJECTIVES--To estimate the prevalence of dementia in an elderly rural population and to determine the effects of age, sex, and education. METHODS--To obtain prevalence estimates of both cognitive impairment and dementia a door to door two phase population survey was carried out in three rural villages in central Italy. Of 1147 inhabitants older than 64, 968 (84.4%) completed the protocol. RESULTS--The prevalence rates (cases per 100 population over 64) were 8.0 for dementia and 27.3 for cognitive impairment. The prevalence rate for dementia did not differ between men and women (7.9 v 8.2), but increased with age (from 1.1 at age 65-69 to 34.8 at age 90-96). Subjects with less than three years of schooling had a significantly higher prevalence of dementia (14.6; 95% confidence interval (95% CI) 10.2-19.1) than subjects with three or more years of schooling (5.9; 95% CI 4.2-7.7). At the multivariate logistic analysis, the risk related with a low level of education was still present after adjustment for age and sex (OR = 2.0; 95% CI 1.2-3.3). Alzheimer's disease was diagnosed in 64% of the 78 demented patients, vascular dementia in 27%, and other dementing diseases in 9%. CONCLUSIONS--In both Alzheimer and vascular dementia subtypes, the prevalence rates did not differ between men and women, but increased with age and were higher in subjects with a low level of education.
PMCID: PMC1073945  PMID: 8648328
8.  Prevalence and outcome of symptomatic carotid lesions in young adults. National Research Council Study Group. 
BMJ : British Medical Journal  1995;310(6991):1363-1366.
OBJECTIVE--To estimate the prevalence and outcome of symptomatic internal carotid artery lesions in young adults. DESIGN--Multicentre hospital based observational study with five year follow up. SETTING--Seven neurological departments in northern and central Italy. SUBJECTS--240 patients (115 men) aged 15-44 with a recent transient ischaemic attack or stroke in the carotid territory. MAIN OUTCOME MEASURES--(a) Prevalence of symptomatic internal carotid artery stenosis or occlusion detected by continuous wave Doppler ultrasonography at entry; (b) incidence rates of cerebral, cardiac, and non-vascular death; non-fatal stroke; and non-fatal myocardial infarction. RESULTS--Carotid stenoses of 50-99% and occlusions were found in 38 patients (15.8%). Both conditions were significantly more frequent in patients aged over 35 and in those with hypertension, diabetes mellitus, and stroke at entry. The standardised mortality ratio at five years was 10.5 (95% confidence interval 5.0 to 19.3). Survival of patients with stenoses of 0-49% and occlusions was significantly better than that of patients with stenoses of 50-99%. Carotid stenosis of 50-99% was an independent predictor of death (hazard ratio 7.9; 95% confidence interval 2.2 to 29) and non-fatal stroke (hazard ratio 7.4; 1.5 to 37.4). CONCLUSIONS--The prevalence of carotid stenosis or occlusion in young adults after a cerebrovascular event is low. Though patients with high grade symptomatic carotid stenosis are at risk of non-fetal and fetal events, patients with internal artery occlusion apparently have a benign prognosis.
PMCID: PMC2549745  PMID: 7787538

Results 1-8 (8)