Protumorigenic effects of mir-145 loss in malignant pleural mesothelioma.

We identified a discrete number of microRNAs differentially expressed in benign or malignant mesothelial tissues. We focused on mir-145 whose levels were significantly downregulated in malignant mesothelial tissues and malignant pleural mesothelioma (MPM) cell lines as compared to benign tissues (pleura, peritoneum or cysts). We show that promoter hyper-methylation caused very low levels in MPM cell lines and specimens. Treatment of MPM cell lines with mir-145 agonists negatively modulated some protumorigenic properties of MPM cells, such as clonogenicity, cell migration and resistance to pemetrexed treatment. The main effector mechanism of the clonogenic death induced by mir-145 was that of accelerated senescence. We found that mir-145 targeted OCT4 via specific binding to its 3'-UTR. Increased intracellular levels of mir-145 decreased the levels of OCT4 and its target gene ZEB1, thereby counteracting the increase of OCT4 induced by pemetrexed treatment which is known to favor the development of chemoresistant cells. In line with this, reintroduction of OCT4 into mimic-145 treated cells counteracted the effects on clonogenicity and replicative senescence. This further supports the relevance of the mir-145-OCT4 interaction for the survival of MPM cells. The potential use of mir-145 expression levels to classify benign vs malignant mesothelial tissues and the differences between pemetrexed-induced senescence and that induced by the re-expression of mir-145 are discussed.

miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer.

Micro RNAs (miRs) are small non-coding RNAs aberrantly expressed in human tumors. Here, we aim to identify miRs whose deregulated expression leads to the activation of oncogenic pathways in human gastric cancers (GCs). Thirty nine out of 123 tumoral and matched uninvolved peritumoral gastric specimens from three independent European subsets of patients were analyzed for the expression of 851 human miRs using Agilent Platform. The remaining 84 samples were used to validate miRs differentially expressed between tumoral and matched peritumoral specimens by qPCR. miR-204 falls into a group of eight miRs differentially expressed between tumoral and peritumoral samples. Downregulation of miR-204 has prognostic value and correlates with increased staining of Bcl-2 protein in tumoral specimens. Ectopic expression of miR-204 inhibited colony forming ability, migration and tumor engraftment of GC cells. miR-204 targeted Bcl-2 messenger RNA and increased responsiveness of GC cells to 5-fluorouracil and oxaliplatin treatment. Ectopic expression of Bcl-2 protein counteracted miR-204 pro-apoptotic activity in response to 5-fluorouracil. Altogether, these findings suggest that modulation of aberrant expression of miR-204, which in turn releases oncogenic Bcl-2 protein activity might hold promise for preventive and therapeutic strategies of GC.

SASP mediates chemoresistance and tumor-initiating-activity of mesothelioma cells.

Here we show that pemetrexed-treated mesothelioma cells undergo accelerated senescence. This is characterized by the secretion of proinflammatory and mitogenic cytokines, reminiscent of an SASP (senescence-associated secretory phenotype). Conditioned media from senescent MPM (malignant pleural mesothelioma) cells trigger the emergence of EMT (epithelial-to-mesenchymal)-like, clonogenic and chemoresistant cell subpopulations, expressing high levels of ALDH (aldehyde dehydrogenase) activity (ALDH(bright) cells). We show by fluorescence-activated cell sorting of purified ALDH(bright) and ALDH(low) cells, that both cell-autonomous and cell-non-autonomous mechanisms converge to maintain the SASP-induced, EMT-like cell subpopulations. Chemoresistant ALDH(bright) cells exist within primary MPM specimens and enrichment for ALDH(bright) cells correlates with an earlier tumor onset into NOD/SCID mice. We show that RAS(v12) expression induces SASP-like changes in untransformed human mesothelial cells, and that p53 ablation increases the effect of RAS(v12) expression. We identify STAT3 activation as a crucial event downstream to SASP signaling. In fact, small hairpin RNA-mediated ablation of STAT3 deeply attenuates the induction of EMT genes and the increase of ALDH(bright) cells induced by SASP-cytokines. This strongly affects the chemoresistance of MPM cells in vitro and leads to anticancer effects in vivo.

[Surgical treatment of spontaneous pneumothorax: comparison of thoracotomy and thoracoscopy]. / Trattamento chirurgico del pneumotorace spontaneo: toracotomia e toracoscopia a confronto.

The video-thoracoscopic treatment of spontaneous pneumothorax currently has the same role of laparoscopic cholecystectomy in abdominal surgery. The Authors consider thoracoscopic approach and traditional thoracotomy examining advantages versus disadvantages, comparing 50 patients with spontaneous pneumothorax treated by thoracoscopy, from February 1992 up to February 1995, and 50 patients, previously treated by open surgery. Video-thoracoscopy has the same percentage of recurrences of thoracotomic approach but assures a quicker functional recovery and, above all, a remarkable reduction of pain.

[Pleuroscopy and talc pleurodesis in recurrent pleural effusions: experience with 51 cases]. / Pleuroscopia e talcaggio nei versamenti pleuric recidivanti: esperizena su 51 casi.

From January '92 up to January '94 thoracoscopy was performed in 51 patients with recurrent pleural effusion: 49 of these patients underwent talc pleurodesis. 10 pleural mesotheliomas, 29 diffuse metastasic pleural involvement and 12 benign effusions were diagnosed. Intrapleural talc therapy allowed a definitive pleurodesis in 43 patients with a success rate of 87%.

[Tracheal resection-anastomosis in carcinoma of the thyroid infiltrating the airways. A case report]. / Resezione--anastomosi tracheale per carcinoma della tiroide infiltrante la via aerea. Caso clinico.

The Authors report a case of thyroid carcinoma with tracheal involvement. Since the neoplastic invasion of the trachea was 3 cm long total thyroidectomy with sleeve tracheal resection and immediate reconstruction with end-to-end anastomosis were performed. The diagnostic and therapeutic approach is discussed and the Literature data reviewed.

[Leiomyosarcoma of the inferior vena cava: description of a new case and review of the literature]. / Leiomiosarcoma della vena cava inferiore: descrizione di un nuovo caso e revisione della letteratura.

A case of primary leiomyosarcoma of the inter-renal vena cava is reported. This tumor is rare and up to date no more than 100 cases have been reported. Surgical treatment consisted in the removal of vena cava from the iliac veins to the suprahepatic veins with right nephrectomy. Restoration of vena cava and left renal vein continuity was not necessary because of the presence of collateral venous circulation at the time of operation. Venous ligation was haemodynamically well tolerated and the patient is disease-free at one year from operation. However, despite surgical radicality, prognosis remains poor given the frequency of metastases reported in more than 35% of cases.

[Low anterior resection of the rectum using mechanical anastomosis in intestinal endometriosis]. / Resezione anteriore bassa del retto con anastomosi meccanica per endometriosi intestinale.

A case of sigmoid-rectal endometriosis prompted the authors to focus attention on the question of indications for surgery and operative tactics in intestinal endometriosis. In this case, the presence of a pelvic mass which could not be cut away from the intestinal wall without the risk of perforation led to the performance of a low anterior resection of the rectum with mechanical stapler, a choice which was certainly radical but necessary in view of the impossibility of excluding the malignant nature of the mass either macroscopically or extemporaneously.

[Malignant mesothelioma located in the pleura: its radical surgical treatment]. / Il mesotelioma maligno localizzato della pleura: trattamento chirurgico radicale.

The authors report a rare case of localized malignant pleural mesothelioma infiltrating the thoracic wall. The absence of widespread pleural involvement allowed for a radical operation with removal of a large portion of the thoracic wall. However, due to rarity of such tumor, an hypothesis on long term prognosis is difficult to formulate.