20 research outputs found
De la Grossesse à la période post-accouchement: stabilité et évolution des représentations maternelles
No full textPer una rilettura dell’infanzia. Progetto di ricerca nei nidi e nelle scuole dell’infanzia di Roma e provincia
No full textBone metastatic process of breast cancer involves methylation state affecting E-cadherin expression through TAZ and WWOX nuclear effectors
No full textWe investigated the involvement of Hippo-related pathways in bone metastasis from breast cancer, by evaluating E-cadherin expression downstream of WWdomain-containing oxidoreductase (Wwox) and transcriptional co-activator with PDZ-binding motif (TAZ). These nuclear effectors functioned in a context-specific fashion on transcriptome, depending on breast-cancer aggressiveness and methylation state. Wwox and E-cadherin were found in human specimens of bone metastasis but not in primary-ductal breast carcinoma, while TAZ showed a characteristic localisation in metastasis nuclei. Wwox and E-cadherin were higher in 1833-metastatic clone with bone avidity than in parental-MDA-MB231 cells, while only metastatic cells presented TAZ. In 1833 cells, a complex interplay of transcriptional signalling controlled E-cadherin transactivation. Wwox and TAZ activated Hypoxia inducible factor-1 (HIF-1) binding to E-cadherin promoter, while Peroxisome proliferator-activated receptor gamma (PPAR gamma) intervened in E-cadherin transactivation favouring and preventing Wwox and TAZ functions, respectively. Methylation impinged on Hippo-related pathways through Wwox and TAZ, modifying metastatic phenotype. The protract exposure to 5-azacytidine (Aza), by affecting methylation state modified the shape of 1833 cells, becoming mesenchymal as that of MDA-MB231 cells and reduced spontaneous-Matrigel invasion. The underlying-molecular mechanisms were diminutions of E-cadherin, Wwox, matrix metalloproteases 2 and 9, HIF-1- and PPAR gamma-activities, inversely correlated to Snail and nuclear-TAZ accumulations. Exogenous WWOX restored 1833-Aza invasion. Thus, 1833-Aza cells permitted to study the role played by methylation in metastasis plasticity, being E-cadherin loss part of an entire-gene reprogramming. Of note, bone-metastasis formation in 1833-Aza xenograft was partially impaired, prolonging mice survival. In conclusion, the methylation-heritable changes seemed important for cancer progression to establish bone metastasis engraftment/growth, by affecting steps requiring homotipic and/or heterotypic-adhesive properties and matrix degradation
Salvage revision surgery after inappropriate approach for primary spine tumors: long term follow-up in 56 cases
No full textBackground: The mainstay treatment of primary malignant bone tumors is wide surgery in the spine. Unfortunately, most cases undergo the first approach in a nonspecialized center; this often means adopting an inappropriate approach with contamination, which consistently decreases the effectiveness of a second surgery. The aim of the present paper is to evaluate recurrence and survival rates after en-bloc resection.
Methods: All patients underwent wide resection by the senior author from January 1997 to December 2013 after the first inappropriate approach was reviewed. Fifty-six patients were included in the present evaluation. Epidemiologic and clinical characteristics, surgeries, early and late complications, and survival rate were reported.
Results: The margin obtained was wide, marginal, and intralesional in 9, 28, and 19 cases, respectively. The complication rates were 55.4% and 44.6% for early and late complications, respectively. Most (73.2%) of the patients had complications. The survival rate is 82.1% at 1 year and then decreases 10% each year until 42.1% at 5 years from surgeries. No statistically significant correlation was found between margin and local recurrence and survival.
Conclusion: In our series, the first inappropriate approach had already compromised patient prognosis, so in case of suspicious primary spine tumor, the patient had to be referred to a specialized center. The margin obtained during salvage surgery does not appear to influence recurrence and survival, probably because it is already compromised by the first surgery. More prospective studies are necessary to confirm our data and verify the impact of the margin obtained during salvage surgery on patients' survival
Epithelioid hemangioendothelioma of the spine: results at seven years of average follow-up in a series of 10 cases surgically treated and a review of literature
No full textPurpose
To review a series of ten cases with epithelioid hemangioendothelioma of the spine, that have undergone surgery to describe clinical presentation, results and complications associated with surgical treatment; a review of literature reporting the main characteristics of the cases already published has been reported.
Methods
A review of patients affected by epithelioid hemangioendothelioma surgically treated by the senior author from 1995 to 2012 was carried out. Ten cases were identified and clinical and radiological characteristics, therapy, complications and survival were valued.
Results
Wide margin was achieved in two out of ten cases, marginal margin in seven and intralesional margin in one case. Average intraoperative blood loss was about 2,800 ml. Reported complications were one case of cord injury, one of dural tear, two cases of massive blood loss, a case of reconstruction failure, a wound dehiscence with deep infection, a pneumonia episode and a deep vein thrombosis with pulmonary embolism. Average follow-up was 84.4 months. Two local recurrences, after 32 and 37 months and two deaths for metastasis, after 14 and 36 months, were reported. Although several chemotherapy protocols are available for the treatment of EH of soft tissue, they are not relevant for the bone.
Conclusions
Wide surgery is probably associated with a better prognosis. Indeed most deaths and local recurrences reported in literature happened after intralesional surgery or chemotherapy/RT alone. The presenting study suggests that the best approach to achieve long-term local control and a major survival could be wide surgery, nevertheless more cases series are necessary to verify survival rate
Hypoxia inducible factor-1 is activated by transcriptional co-activator with PDZ-binding motif (TAZ) versus WWdomain-containing oxidoreductase (WWOX) in hypoxic microenvironment of bone metastasis from breast cancer
No full textThe hypoxic microenvironment of bone marrow favours the bone metastasis process. Hypoxia inducible factor (HIF)-1α is hallmark for hypoxia, correlating with poor prognosis and radio/chemotherapy resistance of primary-breast carcinoma. For bone metastasis, the molecular mechanisms involved in HIF-1α expression and HIF-1 (α/β heterodimer)-transcription factor activity are scarcely known. We studied the role played by HIF-1 in the cross-talk between neoplastic and supportive-microenvironmental cells. Also, WWdomain-containing oxidoreductase (Wwox) and transcriptional co-activator with PDZ-binding motif (TAZ) were taken into consideration evaluating whether these Hippo-pathway effectors affect bone-metastatic phenotype through HIF-1 activity. Considering bone-metastasis specimens, nuclear HIF-1α-TAZ co-localisation occurred in neoplastic and supportive cells, such as fibroblasts and endotheliocytes. Based on these data, the functional importance was verified using 1833-bone metastatic clone under hypoxia: nuclear HIF-1α and TAZ expression increased and co-immunoprecipitated, activating HIF-1-DNA binding and transactivation. In contrast, Wwox localised at perinuclear level in neoplastic cells of bone metastasis, being almost absent in supportive cells, and Wwox-protein expression diminished in hypoxic-1833 cells. Thus, TAZ regulation of HIF-1 activity might be important for bone-secondary growth, participating in metastasis-stroma cross-talk. Further, TAZ and HIF-1α-protein levels seemed correlated. In fact, blocking cyclooxygenase-2 with NS398 in hypoxic-1833 cells, not only HIF-1α decreased but also molecular-mechanism(s) upstream of the Hippo pathway were triggered: LATS-dependent TAZ phosphorylation seemed responsible for TAZ nucleus/cytoplasm translocation and degradation. In the 1833-xenograft model, NS398 largely prevented the outgrowth of bone-metastatic cells, probably related to remarkable-extracellular matrix assembly. We gained clinical insight into HIF-1α and TAZ as candidate biomarkers for bone avidity, relevant for early-therapeutic intervention against bone metastasis
High SPARC Expression Starting from Dysplasia, Associated with Breast Carcinoma, Is Predictive for Bone Metastasis without Enhancement of Plasma Levels
No full textIn order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ETAR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ETAR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ETAR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer
Protesi modulare nelle resezioni di omero prossimale
No full textL’esperienza ultratrentennale dei primi tre Centri Italiani di riferimento per la pato-
logia oncologica muscoloscheletrica viene esposta in questo lavoro sulla protesi
modulare dopo resezioni dell’omero prossimale. I 369 casi raccolti costituiscono la
più vasta casistica internazionale presentata. Ne sono stati esaminati gli aspetti rela-
tivi alla patologia, solo eccezionalmente non oncologica, ed alle caratteristiche pro-
tesiche. Inoltre sono stati considerati i risultati, le complicazioni e gli esiti funziona-
li a distanza
Is the Posterior-Only Approach Sufficient for Treating Cervical Spine Metastases? The Evidence from a Case Series
No full textObjectives: Few studies have evaluated surgical options in the treatment of cervical metastatic disease. The aim of this study is to report the surgical outcomes of patients treated with the posterior-only approach for metastatic cervical disease. Methods: In this retrospective analysis, all cases treated in our institution from 2009 to 2017 were reviewed. Six (20%) patients had intracompartimental lesions (Tomita 1–3), whereas 24 (80%) patients had extracompartimental lesions (Tomita 4–7), with extensive anterior column involvement. All patients were surgically treated with laminectomy and posterior stabilization. Pain and neurologic function were evaluated before and after surgery. Results: Thirty patients were included (15 female, 15 male), with a mean age of 60.6 ± 11.56 years (range 35–82 years). Lesions were located in 7 patients (23.3%) in the upper cervical spine and in 14 patients (46.6%) and in 9 patients (30,1%) in the mid-cervical and in the cervicothoracic junction, respectively. At a mean follow up of 13.7 ± 14.8 months, 15 (50%) patients died from their disease. Pain decreased in all patients after surgery, (preoperative NRS 5.57 ± 1.81 postoperative Numeric Rating Scale of 2.1 ± 1.0, P < 0.00001). Two patients (6.7%) had significant neurologic worsening after surgery. Two (6.9%) patients had surgical-site infection that required reintervention. No mechanical failures were observed. Conclusions: In our series, posterior-only fixation provided postoperative pain relief and achieve spinal stability, ultimately improving the quality of life. In conclusion, posterior-approach decompression and stabilization is a safe and feasible procedure in patients with neurologic or mechanical instability for cervical spine metastasis
