MicroRNA-128-3p-mediated depletion of Drosha promotes lung cancer cell migration

Alteration in microRNAs (miRNAs) expression is a frequent finding in human cancers. In particular, widespread miRNAs down-regulation is a hallmark of malignant transformation. In the present report, we showed that the miR-128-3p, which is up-regulated in lung cancer tissues, has Drosha and Dicer, two key enzymes of miRNAs processing, as the main modulation targets leading to the widespread down-regulation of miRNA expression. We observed that the miRNAs downregulation induced by miR-128-3p contributed to the tumorigenic properties of lung cancer cells. In particular, miR- 128-3p-mediated miRNAs down-regulation contributed to aberrant SNAIL and ZEB1 expression thereby promoting the epithelial-to-mesenchymal transition (EMT) program. Drosha also resulted to be implicated in the control of migratory phenotype as its expression counteracted miR-128-3p functional effects. Our study provides mechanistic insights into the function of miR-128-3p as a key regulator of the malignant phenotype of lung cancer cells. This also enforces the remarkable impact of Drosha and Dicer alteration in cancer, and in particular it highlights a role for Drosha in non-smallcell lung cancer cells migration

Radioterapia intraoperatoria nei tumori maligni avanzati estesi all’orecchio medio: valutazione da uno studio retrospettivo

Obiettivo dello studio è stato quello di valutare la sicurezza, l’efficacia e i risultati funzionali della radioterapia intraoperatoria (IORT) seguita dalla radioterapia a intensità modulata (IMRT) nel trattamento di tumori maligni avanzati estesi all’orecchio medio. Sono stati inclusi nello studio in modo retrospettivo 13 pazienti consecutive affetti da tumore dell’orecchio esterno esteso all’orecchio medio. Il follow-up è stato in media di 33 mesi (range 6-133). Cinque pazienti (38%) erano di stadio III e 8 pazienti (62%) erano di stadio IV secondo la classificazione dell’Università di Pittsburgh. Una petrosectomia laterale (LTBR) è stata eseguita in tutti i pazienti, la LTBR è stata associata a parotidectomia in 5 (38%) casi e a svuotamento latero-cervicale associato a parotidectomia in 6 (46%) casi. In tutti i casi si è effettuata asportazione della malattia macroscopicamente evidente. Il trattamento chirurgico è stato completato da IORT (12 Gy) e IMRT (50Gy). Chemioterapia adiuvante è stata eseguita in 4 (30%) casi. Test audiometrici pre- e post-operatori sono stati eseguiti per valutare la perdita uditiva. Il tasso di controllo di malattia locale (LC) a 5 anni, di metastasi a distanza (DM) a 5 anni, la sopravvivenza libera da malattia (DFS) e la sopravvivenza globale (OS) a 5 anni sono state calcolate con il metodo di Kaplan-Meyer. Variazioni significative nella conduzione per via ossea sono state osservate dopo trattamento. Una necrosi parziale del lembo di ricostruzione è stata l’unica complicanza precoce osservata in 3(23%) casi, mentre una fistola meningea è stata osservata in un solo caso (7,6%) come complicanza tardiva. Il tasso di LC è stato del 68%. Il tasso di DM è stato del 90%. Il tasso di DFS è stato del 61%. Il tasso di OS è stato del 69%. La IORT seguita dalla IMRT nel trattamento dei tumori maligni avanzati dell’orecchio esterno e medio sembra essere sicuro. Nel nostro studio non sono riportati morti. La IORT può ridurre la dose di radioterapia postoperatoria a livello del tessuto residuo ottenendo la medesima dose a livello della sede del tumore. Non abbiamo osservato alcuna complicanza a livello dell’orecchio esterno residuo, mentre si è notato un peggioramento dell’udito anche a livello neurosensoriale. Sono necessari studi prospettici al fine di confermare quanto da noi osservato

Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation

<p>Abstract</p> <p>Background</p> <p>In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m²weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting.</p> <p>Methods</p> <p>40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m²to 100 mg/m². Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.</p> <p>Results</p> <p>Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine.</p> <p>Conclusion</p> <p>Low-dose fotemustine at 65–75 mg/m²(induction phase) followed by 75–85 mg/m²(maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.</p

Diffusion and perfusion weighted magnetic resonance imaging for tumor volume definition in radiotherapy of brain tumors

Abstract Accurate target volume delineation is crucial for the radiotherapy of tumors. Diffusion and perfusion magnetic resonance imaging (MRI) can provide functional information about brain tumors, and they are able to detect tumor volume and physiological changes beyond the lesions shown on conventional MRI. This review examines recent studies that utilized diffusion and perfusion MRI for tumor volume definition in radiotherapy of brain tumors, and it presents the opportunities and challenges in the integration of multimodal functional MRI into clinical practice. The results indicate that specialized and robust post-processing algorithms and tools are needed for the precise alignment of targets on the images, and comprehensive validations with more clinical data are important for the improvement of the correlation between histopathologic results and MRI parameter images

Data for: Open kyphoplasty for metastatic spine disease: A retrospective clinical series

rough data about open kyphoplast

Data for: Open kyphoplasty for metastatic spine disease: A retrospective clinical series

rough data about open kyphoplastyTHIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Data for: Schwannomas of the sciatic nerve: a rare and neglected diagnosis. A review of the literature with two illustrative cases.

review of the literature of sciatic schwnnomas in the last 30 year