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Biomedical subjects

E Martinelli

Publications and source records attributed to E Martinelli.

At least 19 recordsLinked to original sources
PubMed2007

Tissue factor and vascular endothelial growth factor expression in colorectal cancer: relation with cancer recurrence.

OBJECTIVE: This study was undertaken to quantify tissue factor (TF) and vascular endothelial growth factor (VEGF) in colorectal cancer and to evaluate their possible relationship with recurrence. METHOD: TF and VEGF were measured by enzyme-linked immunosorbent assay in surgical tumour specimens and normal mucosa from 50 consecutive patients with colorectal cancer who were followed up for 3 years for the assessment of disease recurrence. RESULTS: TF and VEGF antigens were detected in all tumour samples. VEGF, but not TF, was much higher in tumour than in normal mucosa (P < 0.0001), as also confirmed by measurement of specific mRNAs. There was a strong correlation between TF and VEGF antigens (P < 0.0005) in tumour tissue but not in normal mucosa. Neither protein was related to tumour stage, grade or size. Local or distant recurrence was statistically related to pTNM stage. High VEGF, but not TF, levels in tumour extracts were associated with an increased risk of recurrence both by univariate (RR, 4.00, 95% CI: 1.45-11.0) and multivariate analyses (RR, 3.65, 95% CI: 1.33-10.0). CONCLUSION: These findings suggest that VEGF content in colorectal cancer is an independent risk factor for tumour recurrence and might help select patients who might benefit from adjuvant therapy.

Colorectal Neoplasms↗
PubMed2006

Weekly docetaxel and capecitabine is not effective in the treatment of advanced gastric cancer: a phase II study.

BACKGROUND: Capecitabine and docetaxel have demonstrated preclinical antitumor synergy and activity in advanced gastric cancer. We assessed the clinical activity and the toxicity of weekly docetaxel in combination with capecitabine in untreated patients with advanced gastric cancer. PATIENTS AND METHODS: A total of 38 patients were treated with docetaxel 36 mg/m2 on days 1, 8, and 15 i.v., plus capecitabine, 625 mg/m2 bid per os on days 5 to 18 repeated every 4 weeks. RESULTS: All patients were assessable for response to treatment and for toxicity. Major responses were observed in eight patients (21%), with three patients achieving a CR (7.8%) and five showing a PR (13%). The median time to progression was 5.4 months and the overall survival was 7.7 months. The safety profile of this schedule was acceptable with a low rate of myelossuppression, diarrhoea and hand-foot syndrome. CONCLUSIONS: The combination of docetaxel and capecitabine at the doses and schedule investigated in this study is safe, but does not show significant activity in untreated patients with advanced gastric cancer.

Adenocarcinoma↗
PubMed2006

De novo pure 12q22q24.33 duplication: first report of a case with mental retardation, ADHD, and Dandy-Walker malformation.

We present a patient with a de novo 12q nonmosaic pure duplication characterized by multiple minor anomalies and Dandy-Walker malformation. A neurological and behavioral assessment revealed psychomotor retardation and attention deficit/hyperactivity disorder (ADHD), with neurobehavioral abnormalities (auto- and heteroaggressive behavior). Fluoxetine therapy in this case markedly improved the neurobehavioral profile, with a decreased level of aggression. To define the extension of the duplicated region, we performed FISH analyses by using YAC probes. The analyses revealed a tandem duplication of the 12q22q24.33 region, with the proximal breakpoint located between 96.5 and 97.6 cM and the distal one between 154 and 161 cM. This is the first case of pure de novo duplication involving the 12q22q24.33 region. To better define the clinical phenotype associated with 12q partial duplication, we compared our case with the four patients with similar pure duplications previously described.

Abnormalities, Multiple↗
PubMed2006

Interaction between the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) pathways: a rational approach for multi-target anticancer therapy.

Over the last decade, the concept of targeted biological therapy for the treatment of cancer has emerged. However, a better understanding of these targets and their role in tumor cells and in the surrounding stromal cells is required. Two interesting biological targets are the epidermal growth factor receptor (EGFR) and the vascular endothelia growth factor (VEGF) and its receptors. A number of agents that target these pathways have been described. Many of these are currently in clinical trials and a few have recently been approved by the regulatory authorities in USA and in the European Union. The molecular pathways involved in the proliferation of cancer cells and in tumor-related angiogenesis are very complex and the interference with only a single step of these pathways may often reveal an insufficient therapeutic approach. Moreover, cancer cells have an inherent ability to harness different growth factor signaling pathways for growth advantage and cell survival, a process that may even be facilitated by the use of selective targeted agents. Because of these escape mechanisms, monotherapy with selective targeted agents is unlikely to be a fully effective cancer treatment. For these reasons, targeting different pathways is an attractive and effective therapeutic strategy with a strong rationale for investigating this approach in the clinic. This review focuses on the preclinical rationale of combining targeted agents such as EGFR and VEGF inhibitors in the treatment of cancer and on the clinical trials that have emerged from these studies.

Animals↗
PubMed2005

Survivin expression in ovarian cancer and its correlation with clinico-pathological, surgical and apoptosis-related parameters.

We investigated the association of survivin expression with prognosis and other apoptosis-related biological factors in 110 primary ovarian cancer patients admitted to the Division of Gynecologic Oncology, Catholic University of Rome. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections by using polyclonal antibody ab469 for survivin, and mouse monoclonal antibodies (clone 124 and DO-7), for bcl-2 and p53, respectively. Cytoplasmic survivin immunoreaction was observed in 84.5% cases, while nuclear survivin immunostaining was observed in 29.1% cases. We failed to find any relationship between cytoplasmic survivin positivity rate and any of the parameters examined. Serous tumours showed a lower percentage of nuclear survivin positivity with respect to other histotypes (20.5 vs 48.6%, respectively; P-value=0.004). The percentage of nuclear survivin positivity was higher in cases subjected to primary tumour cytoreduction (43.5%), with respect to patients subjected to exploratory laparotomy (20%) (P=0.024). Bcl-2 and p53 were, respectively, expressed in 27.3 and 60.0% of the cases and their expression was not correlated with survivin status. During the follow-up period, progression and death of disease were observed in 68 (61.8%) and 53 (48.2%) cases, respectively. There was no difference in time to progression and overall survival according to survivin status in ovarian cancer patients. In conclusion, in our experience, the immunohistochemical assessment of survivin status does not seem to be helpful in the prognostic characterisation of ovarian cancer. A more in depth investigation of the complex physiology of divergent survivin variants is needed in order to clarify the biological and the clinical role of differentially located survivin isoforms.

Apoptosis↗
PubMed2004

[Preclinical and clinical results with the epidermal growth factor receptor inhibitor Gefitinib (ZD1839, Iressa)].

Since epidermal growth factor receptor (EGFR) is involved in tumor proliferation and angiogenesis, and in the mechanisms of resistance to chemo- and hormono-therapy, it represents a unique promising target for anticancer treatment. Gefinitib (Iressa, ZD1839), an inhibitor of the EGFR tyrosine kinase activity able to bind the intracellular domain of the receptor, is at present in clinical development. In preclinical models Gefitinib induced a dose-dependent response rate in tumor xenografts obtained from different human cancer cells lines. The expression of EGFR in the prior tumor did not appear to be a predictive marker for Gefitinib sensitivity. Furthermore, long-term drug use was well tolerated in mice without inducing resistance. However, tumors started to grow again after treatment interruption. Laboratory findings and in vivo data have prompted the evaluation of Gefitinib administered as a single oral daily dose alone or in combination with conventional anticancer treatment.

Animals↗
PubMed2004

Monitoring of biological odour filtration in closed environments with olfactometry and an electronic nose.

Air treatment with a compact biological membrane filter, and air quality monitoring with an electronic nose were tested in the laboratory on air from a cage containing six mice. Additional analyses of air to and from the filter were performed using olfactometry and ammonia and hydrogen sulphide gas detection tubes. The biological air filter is a module containing biofilm-coated membrane fibres that separate a closed liquid loop from a gas phase. Odour compounds and oxygen diffuse through the membranes from the gas phase to the biofilm, where they are degraded to carbon dioxide and water. The prototype "ENQBE" electronic nose is based on an array of eight thickness shear mode resonators (TSMR), also known in the literature as quartz microbalance sensors. The chemical sensitivity is given by molecular films of metalloporphyrins and similar compounds. Chemical interaction of compounds in the air with the vibrating sensors induces a frequency change of the vibration that can be measured as a signal. The air from the mouse cage had a strong odour (3490 OUE/m3). The biological membrane filter performed well, achieving over 80% odour and ammonia reduction. The electronic nose signal could be correlated with the inlet and outlet air-quality of the biological filter, making it a promising method for monitoring air quality in closed environments.

Air Pollutants↗
PubMed2003

Resistive load of laryngeal mask airway and ProSeal laryngeal mask airway in mechanically ventilated patients.

BACKGROUND: The ProSeal Laryngeal Mask Airway (PLMA) ventilation tube is narrower and shorter than the standard Laryngeal Mask Airway (LMA) and is without the vertical bars at the end of the tube. In this randomized, crossover study, PLMA and LMA resistances were compared. METHODS: Respiratory mechanics was calculated in 26 anesthetized, mechanically ventilated patients with both LMA and PLMA. The laryngeal mask positioning was fiberoptically evaluated. Differences in the respiratory mechanics of the LMA and the PLMA were attributed to the differences between the laryngeal masks. RESULTS: In the total study population the airway resistance was 1.5 +/- 2.6 hPa.l-1.s-1 (P = 0.005) higher with the PLMA than with the LMA. During the PLMA use, the peak expiratory flow reduced by 0.02 +/- 0.05 l min-1 (P = 0.046), the expiratory resistance increased by 0.6 +/- 1.3 hPa.l-1.s-1 (P = 0.022), and the time constant of respiratory system lengthened by 0.09 +/- 0.18 s (P = 0.023). These differences doubled when the LMA was better positioned than the PLMA, whereas they disappeared when the PLMA was positioned better than the LMA. CONCLUSIONS: The standard LMA offers a lower resistive load than the PLMA. Moreover, the fitting between the laryngeal masks and the larynx, as fiberoptically evaluated, plays a major role in determining the resistive properties of these devices.

Adult↗
PubMed2001

p63 identifies keratinocyte stem cells.

The proliferative compartment of stratified squamous epithelia consists of stem and transient amplifying (TA) keratinocytes. Some polypeptides are more abundant in putative epidermal stem cells than in TA cells, but no polypeptide confined to the stem cells has yet been identified. Here we show that the p63 transcription factor, a p53 homologue essential for regenerative proliferation in epithelial development, distinguishes human keratinocyte stem cells from their TA progeny. Within the cornea, nuclear p63 is expressed by the basal cells of the limbal epithelium, but not by TA cells covering the corneal surface. Human keratinocyte stem and TA cells when isolated in culture give rise to holoclones and paraclones, respectively. We show by clonal analysis that p63 is abundantly expressed by epidermal and limbal holoclones, but is undetectable in paraclones. TA keratinocytes, immediately after their withdrawal from the stem cell compartment (meroclones), have greatly reduced p63, even though they possess very appreciable proliferative capacity. Clonal evolution (i.e., generation of TA cells from precursor stem cells) is promoted by the sigma isoform of the 14-3-3 family of proteins. Keratinocytes whose 14-3-3final sigma has been down-regulated remain in the stem cell compartment and maintain p63 during serial cultivation. The identification of p63 as a keratinocyte stem cell marker will be of practical importance for the clinical application of epithelial cultures in cell therapy as well as for studies on epithelial tumorigenesis.

3T3 Cells↗
PubMed2001

Interleukin-6 serum level correlates with survival in advanced gastrointestinal cancer patients but is not an independent prognostic indicator.

Interleukin-6 (IL-6) is a pleiotropic cytokine that has been shown to regulate immune defense mechanisms and hematopoiesis. In addition, IL-6 may also be involved in malignant transformation and tumor progression. A poor prognosis in patients with multiple myeloma, renal cell carcinoma, ovarian cancer, or prostate cancer has been associated consistently with elevated IL-6 serum levels. The aim of this study was, therefore, to assess IL-6 serum levels in 68 advanced gastrointestinal cancer patients and to correlate them with prognosis. IL-6 serum levels were found to be significantly elevated in cancer patients with respect to controls. Moreover, patients with disseminated cancer displayed significantly higher IL-6 serum levels than patients without apparent metastases. On univariate analysis, both overall survival (OS) and time to disease progression (TTP) were shown to be affected by IL-6 serum levels. However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-6 serum levels while confirming the role of previously established variables, such as performance status, carcinoembryonic antigen (CEA) serum levels, and distant metastases. In conclusion, this study showed that IL-6 serum levels were elevated in advanced gastrointestinal cancer patients and correlated with both OS and TTP. However, they were shown not to be an independent prognostic factor.

Antimetabolites, Antineoplastic↗
PubMed2000

Constipation after hysterectomy: fact or fiction?

Hysterectomy is responsible for numerous postoperative complications largely urological, but sometimes of sexual or colorectal function. The latter involve modifications of bowel function resulting in constipation as a result of delayed transit, infrequent evacuations and greater difficulty in expelling faeces. We have reviewed the topic, and consider the various hypotheses whereby these modifications may result from hormonal alterations, iatrogenic causes, or variations in recto-bladder sensitivity. Any of these could justify the modifications in bowel function detected in these patients. The studies carried out so far provide no clear information about the type of constipation that develops after hysterectomy, as we lack prospective studies that compare bowel function before and after operations. Nor is it clear whether we are dealing with constipation as a result of delayed transit or obstructed defaecation, nor which pathogenetic mechanisms are involved. In view of the large number of hysterectomies that are done, sometimes prophylactically, controlled prospective studies are warranted to address these issues more fully.

Constipation↗
PubMed1999

Slow-transit constipation: solitary symptom of a systemic gastrointestinal disease.

INTRODUCTION: Autonomic neuropathy is thought to play a role in the pathogenesis of slow-transit constipation, but other gastrointestinal organs may also be involved, even if they are symptom-free. We investigated whether motility in gastrointestinal organs other than the colon was impaired in patients with slow-transit constipation and whether the autonomic nervous system was involved. METHODS: Twenty-one consecutive patients (18 females; median age, 46 years) with severe chronic constipation (< or = 2 defecations/week and delayed colonic transit time) were studied. Autonomic neuropathy function was tested with esophageal manometry, gastric and gallbladder emptying (fasting and postprandial motility) by ultrasonography, orocecal transit time (H2-breath test), colonic transit time (radiopaque markers), and anorectal volumetric manometry. The integrity of the autonomic nervous system was assessed by a quantitative sweat-spot test for preganglionic and postganglionic fibers, tilt-table test, and Valsalva electrocardiogram R-R ratio. RESULTS: Esophageal manometry showed gastroesophageal reflux or absence of peristalsis in five of the seven patients examined. Gallbladder dysmotility (i.e., increased fasting, postprandial residual volume, or both) was observed in 6 of 14 (43 percent) patients. Gastric emptying was decreased in 13 of 17 (76 percent) patients. Orocecal transit time was delayed in 18 of 20 (90 percent) patients; median transit time was 160 (range, 90-200) minutes. Median colonic transit time was 97 (range, 64-140) hours. Anorectal function showed abnormal rectoanal inhibitory reflex and decreased rectal sensitivity in 11 of 19 (58 percent) patients. Signs of autonomic neuropathy of the sympathetic cholinergic system were found in 14 of 18 (78 percent) patients. Only one of nine patients had vagal abnormalities detected with the Valsalva test and four of five patients with a history of orthostatic hypotension had a positive tilt-table test. CONCLUSIONS: Slow-transit constipation may be associated with impaired function of other gastrointestinal organs. More than 70 percent of patients with slow-transit constipation present some degree of autonomic neuropathy. Severe constipation may be the main complaint in patients with a systemic disease involving several organs and possibly involving the autonomic nervous system. This should be considered in the management of such cases.

Adolescent↗
PubMed1997

Postoperative changes in serum interleukin-2 concentrations.

OBJECTIVE: To evaluate the postoperative changes in circulating interleukin-2 (IL-2) concentration according to the severity of the surgical injury and other postoperative variables that could influence IL-2 production. DESIGN: Prospective observational study. SETTING: University hospital, Italy. SUBJECTS: 43 patients about to undergo major operations (gastric and colo-rectal resection for cancer), intermediate operations (open cholecystectomy or mastectomy for cancer), and minor operations (hernia repair or breast lump); 24 healthy age and sex matched controls. MAIN OUTCOME MEASURES: Postoperative changes in serum concentrations of IL-2 after different degrees of surgery on the 1st, 3rd and 8th postoperative days correlated with changes in in vivo cellular mediated immunity (skin tests), duration of operation, blood transfusion or postoperative H2-blockers and antiprostaglandins. RESULTS: There were no significant variations in IL-2 serum concentrations postoperatively on ANOVA, and when the data were normalised, there were no significant changes in the median postoperative values after minor and intermediate operations. There was a slight but not significant increase in IL-2 concentrations after major operations. Neither blood transfusion nor duration of operation correlated with postoperative changes in IL-2, while postoperative antiprostaglandins and H2-blockers seemed to provide slight but not significant protection against a reduction in IL-2 concentrations. CONCLUSIONS: Circulating IL-2 does not necessarily correlate with reported in vitro postoperative production of IL-2 and therefore seems to be of little use in monitoring immunosuppression in surgical patients.

Adult↗
PubMed1996

Fast-to-slow muscle conversion by chronic electrostimulation: effects on mitochondrial respiratory chain function with possible implications for the gracilis neosphincter procedure.

The effects of chronic, around the clock, low-frequency electrostimulation on the respiratory chain activity and cytochrome content of freshly isolated mitochondria were evaluated in rabbit skeletal muscle before and after 30 days of continuous or cyclical electrostimulation using a totally implantable system and a training programme now used in humans. The respiratory activity measured in state III increased strongly after electrostimulation. The efficiency of the respiratory chain increased significantly after electrostimulation but the activity of complex [(reduced nicotinamide adenine dinucleotide dehydrogenase) did not increase. The amount of cytochromes a and a3, b562, and c and c1 increased clearly after electrostimulation. The respiratory activity rate of mitochondria obtained after continuous electrostimulation was apparently higher than after cyclical electrostimulation. Chronic uninterrupted low-frequency electrostimulation, using a clinical training programme, induces an increase in mitochondrial respiratory chain activity in purified mitochondria of skeletal muscle. These changes are the basis of induced resistance to fatigue in fast-to-slow muscle conversion by chronic electrostimulation.

Animals↗
PubMed1996

Vaginal repair of rectocele after dynamic graciloplasty for fecal incontinence due to imperforate anus.

A 35-years-old woman developed obstructed defecation due to a large (6 cm) non-emptying rectocele one year after successful electrostimulated gracilis neosphincter operation for correction of fecal incontinence after surgery for imperforate anus. Surgical correction of the rectocele was performed by a trans-vaginal approach due to the poor elasticity of the neoanus and avoidance of possible damage to the neosphincter. After physiological investigations, including defecography, the patient had a resection of the posterior vaginal mucosal wall, a double layer plication of the muscular wall with non-absorbable suture and a longitudinal mucosal suture. The postoperative course was uneventful. Defecography, performed 3 and 6 months later, showed a marked reduction of the rectocele (2 cm) which corresponded to clinical improvement. Occurrence of disabling rectocele can be considered a possible long term complication after successful electrostimulated neosphincter procedure in patients at risk for developing a rectocele; a successful repair can be obtained using trans-vaginal approach without the risk of neosphincter damage. Transvaginal repair of rectocele in similar clinical situations may be recommended.

Adult↗