Prognostic value of soluble P-selectin levels in colorectal cancer

Measurement of soluble (s) P-selectin levels has been proposed as a diagnostic tool for monitoring the clinical course of human neoplasms. Thus, our study was aimed at analyzing the role of sP-selectin in association with clinicopathological variables in 181 patients with primary (n =149) or metastatic (n = 32) colorectal cancer (CRC), 34 patients with benign diseases and 181 control subjects. The results obtained showed that sP-selectin levels were higher in patients with CRC compared either to patients with benign disease (p = 0.006) or controls (p = 0.003). No differences were observed between the latter and patients with benign diseases. Increased median sP-selectin levels were significantly associated with the presence of distant metastasis (68.2 ng/ml vs. 48.6 ng/ml, p = 0.002). Of interest, carcinoembryonic antigen (CEA) levels were independently associated to sP-selectin (regression coefficient = 0.28, p < 0.002). Cox's proportional hazards survival analysis of primary CRC patients demonstrated that beside the stage of disease sP-selectin levels had an independent prognostic role in predicting recurrent disease (HR = 2.22, p = 0.019) and mortality from CRC (HR = 3.44, p= 0.017). These results suggest that measurement of plasma sP-selectin might represent a prognostic indicator in the management of patients with CRC

People meet in Petrzalka. The requalification of a public space in a post-socialist neighborhood

LAUREA SPECIALISTICAIl quartiere di Petrzalka rappresenta per Bratislava ai giorni nostri una problematica urbana ancora aperta. La sua nascita, negli anni ’70, per volere del regime, che ha cancellato completamente una parte di storia della città e del suo passato, imponendo un carattere urbano completamente differente, rappresenta una fase amara ed irrisolta per Bratislava e per i suoi abitanti. Dopo 40 anni di cambiamenti urbani, trasformazioni delle città e l’avvento del nuovo millennio, risulta ancora più evidente quanto l’utopico esperimento urbanistico di quegli anni sia fallito miseramente a Petržalka come in moltissimi altri analoghi quartieri europei. Ad oggi l’area si presenta obsoleta, collegata al resto della città solo dal punto di vista automobilistico, piena di edifici imponenti e massicci, spaesante e fuori scala, priva di punti di riferimento e di spazi pubblici che offrano agli abitanti un abitare di qualità. Oltre ai seri problemi tecnologici e alle carenze di cui soffrono gli edifici, l’area manca completamente di servizi alla persona e spazi di aggregazione; il progetto del verde esistente riguarda soltanto le corti degli edifici e non è pensato a scala di quartiere; mancano delle funzioni di riferimento che possano configurarsi come punti strategici sull’area. Al giorno d’oggi la pianificazione che riguarda Petrzalka ha sempre coinvolto idee progettuali che tendono a “riempire” il vuoto di risulta della pianificazione degli anni ’70, con l’idea di aggiungere nuovi edifici e funzioni mancanti. Il nostro lavoro di ricerca per la riqualificazione parte invece dalla scala umana, dalla valorizzazione del paesaggio e dal recupero dell’identità di quartiere; al contrario dei developers, noi crediamo che l’identità storica ed il futuro di Petrzalka siano nel suo patrimonio verde, nel suo parco, nel suo bosco, così amati dai suoi abitanti e così pieni di potenziale per tutta la città di Bratislava. In relazione a questo, il nostro intento di apportare le funzioni mancanti nell’area si vuole delineare come un intervento silenzioso ma presente, che apporti il nuovo in una gerarchia di scala tra il quartiere e la città, convogliando i flussi all’interno dell’area e scandendo il corso del canale di Petrzalka in una nuova successione diversificata di piccole e grandi polarità. Il nostro lavoro di ricerca, più che offrire una soluzione assoluta e compiuta offre un nuovo punto di vista, un nuovo approccio ad una problematica sull’area sempre aperta e combattuta, con l’idea che la qualità nasce attorno alla persona e da una riduzione di scala che possa creare una nuova identità urbana.What will be the future of Petržalka? Today this issue represents a debate still open. The construction of Petržalka in the 70s,under the socialist regimen, completely cancelled a part of Bratislava’s history, imposing a completely different urban character; Petržalka therefore still stands as a strong symbol for both the city and the citizens. After 40 years of urban changes, transformations and despite the new millennium advent, it is straightforward how the utopist urban experiment of those years miserably failed in that district, as well as in many other European ones. Today the area is obsolete, connected to the rest of the city only through highways and full of massive and out of scale buildings, without reference points or public spaces able to offer a qualified living. Beyond the serious technological problems and weaknesses shown by the buildings, the area misses a lot of services for the inhabitants, as well as aggregation spaces; existing green areas are indeed designed only in the buildings’ courtyards and not at the district scale. Up to now, the planning about Petržalka has always involved design strategies willing to “fill up” the unplanned voids resulting from the concepts of the 70s, according to the idea of adding new buildings and new functions in a big scale. Our research work for the urban requalification of Petržalka focuses on the human scale, based on the value of the existing landscape and on the recovery of the district identity. Opposite to the plans of developers, we believe that Petržalka’s historical identity and future lies in its green heritage, in its park, in its wood, so beloved by its inhabitants and so full of potential for the whole city of Bratislava. In relation to that, our willingness to add functions to the area aims at proposing a silent but relevant intervention, by creating a hierarchy of scale between the district and the city, at the same time channeling flows into the area and marking Petržalka’s watercourse through a sequence of small and big polarities. Our research does not offer an absolute solution, but rather provides a point of view, a new approach to a still open debate, as it stems from the idea that the quality arises around the people and can be generated by a scale reduction which could foster a new urban identity

Liposarcoma of the colon presenting as an endoluminal mass

<p>Abstract</p> <p>Background</p> <p>Liposarcoma is one of the most common soft tissue sarcoma of adult life, usually occurring in the retroperitoneum and the extremities. Primary liposarcoma of the colon is very rare. The optimal treatment has not been established due to the small number of cases reported. We report a case of primary liposarcoma of the colon presenting as a massive intraluminal lesion.</p> <p>Case presentation</p> <p>A 79-year-old woman presented with abdominal pain, progressive constipation and weight loss. A CT scan and a colonoscopy revealed an intraluminal mass in the transverse colon and multiple intraperitoneal lesions. The patient underwent surgical resection of the lesions. Pathologic examination was consistent with pleomorphic liposarcoma of the colon.</p> <p>Conclusion</p> <p>Although no guidelines are available for the management of liposarcoma of the colon, surgical resection should be performed when feasible. Our patient's overall survival was satisfactory in spite of the multiple negative prognostic factors.</p

High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis

<p>Abstract</p> <p>Background</p> <p>Human Leukocyte Antigen (HLA)-E is a non-classical class I HLA molecule that can be stabilized by ligands donated by other classical (HLA-A, -B, -C) and non-classical (HLA-G) family members. HLA-E engages a variety of immune receptors expressed by cytotoxic T lymphocytes (CTLs), Natural killer (NK) cells and NK-CTLs. In view of the opposing outcomes (activation or inhibition) of the different HLA-E receptors, the preferred role (if any) of HLA-E expressed <it>in vivo </it>on tumor cells remains to be established.</p> <p>Methods</p> <p>Taking advantage of MEM-E/02, a recently characterized antibody to denatured HLA-E molecules, HLA-E expression was assessed by immunohistochemistry on an archival collection (formalin-fixed paraffin-embedded) of 149 colorectal primary carcinoma lesions paired with their morphologically normal mucosae. Lymphoid infiltrates were assessed for the expression of the HLA-E-specific, inhibitory, non-rearranging receptor NKG2A.</p> <p>Results</p> <p>High HLA-E expression did not significantly correlate with the expression of classical HLA-B and HLA-C molecules, but it did correlate with high expression of its preferential ligand donor HLA-A. In addition, it correlated with lymphoid cell infiltrates expressing the inhibitory NKG2A receptor, and was an independent predictor of good prognosis, particularly in a subset of patients whose tumors express HLA-A levels resembling those of their paired normal counterparts (HLA-A). Thus, combination phenotypes (HLA-E^lo-int/HLA-AE and HLA-E^hi/HLA-AE) of classical and non-classical class I HLA molecules mark two graded levels of good prognosis.</p> <p>Conclusions</p> <p>These results suggest that HLA-E favors activating immune responses to colorectal carcinoma. They also provide evidence in humans that tumor cells entertain extensive negotiation with the immune system until a compromise between recognition and escape is reached. It is implied that this process occurs stepwise, as predicted by the widely accepted 'immunoediting' model.</p

The mesenchymal stem cell differentiation to osteoblasts is potentiate by the allosteric modulation of A2B adenosine receptors.

The A2B adenosine receptor (A2BAR) has been recently emerged as the major adenosine receptor involved in the mesenchymal stem cell differentiation to osteoblast and bone formation, highlighting this receptor as a new target in bone diseases. In the present study, we characterized a new 3-keto-indole-derivative (KI-7) as the first positive allosteric modulator (PAM) of the human A2B AR in mesenchymal stem cells (MSCs), and we investigated the potential activity of this compound as osteogenic agent. KI-7 was able to increase the effects of A2B AR of both endogenous and orthosteric agonists on the expression of osteogenic markers and on osteoblast mineralization. In the early phase of differentiation program, KI-7 significantly potentiated physiological and A2B agonist-mediated down-regulation of IL-6 release. Conversely, during the late stage of differentiation, when most of the cells have an osteoblast phenotype, KI-7 caused a sustained raise in IL-6 levels and an improvement in osteoblast viability. These data suggest that positive allosteric modulation of A2B AR not only favors MSC commitment to osteoblasts, but also ensures a greater survival of mature osteoblasts. Our study paves the way for a therapeutic use of selective positive allosteric modulators of A2B AR in the control of osteoblast differentiation, bone formation and fracture repair

Association between serum carcinoembryonic antigen and endothelial cell adhesion molecules in colorectal cancer

OBJECTIVES: To analyse the behaviour of pre-surgical serum levels of soluble (s)E-selectin and vascular cell adhesion molecule (sVCAM) in patients with colorectal cancer, and to evaluate their possible correlation with carcinoembryonic antigen (CEA), pro-inflammatory cytokines and clinicopathological features with respect to their prognostic value in predicting metastatic disease. METHODS: Pre-surgical serum levels of sE-selectin, sVCAM, interleukin-6 (IL-6), IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and CEA were measured in 194 patients with colorectal adenocarcinoma, 40 patients with benign colorectal diseases and 59 healthy subjects. RESULTS: sE-selectin, sVCAM, TNF-alpha and IL-6 levels were significantly higher in patients with colorectal cancer compared to either healthy subjects or patients with benign disease. Positive rates of sE-selectin, sVCAM and TNF-alpha levels were significantly associated with Dukes' stage D colorectal cancer, and all three variables were independently associated to the presence of distant metastases. Positive sE-selectin, sVCAM and TNF-alpha levels were significantly associated to CEA. TNF-alpha and CEA levels were independently related to the presence of positive levels of sE-selectin and/or sVCAM. CONCLUSIONS: Our findings suggest that the host inflammatory response to cancer cells, and/or their released products (i.e. CEA), might be responsible (via cytokine release) for the elevation in circulating adhesion molecules in patients with colorectal cancer

TSPO-ligands prevent oxidative damage and inflammatory response in C6 glioma cells by neurosteroid synthesis

Translocator protein 18 kDa (TSPO) is predominantly located in the mitochondrial outer membrane, playing an important role in steroidogenesis, inflammation, cell survival and proliferation. Its expression in central nervous system, mainly in glial cells, has been found to be upregulated in neuropathology, and brain injury. In this study, we investigated the anti-oxidative and anti-inflammatory effects of a group of TSPO ligands from the N,N-dialkyl-2-phenylindol-3-ylglyoxylamide class (PIGAs), highlighting the involvement of neurosteroids in their pharmacological effects. To this aim we used a well-known in vitro model of neurosteroidogenesis: the astrocytic C6 glioma cell line, where TSPO expression and localization, as well as cell response to TSPO ligand treatment, have been established. All PIGAs reduced l-buthionine-(S,R)-sulfoximine (BSO)-driven cell cytotoxicity and lipid peroxidation. Moreover, an anti-inflammatory effect was observed due to the reduction of inducible nitric oxide synthase and cyclooxygenase-2 induction in LPS/IFNγ challenged cells. Both effects were blunted by aminoglutethimide (AMG), an inhibitor of pregnenolone synthesis, suggesting neurosteroids' involvement in PIGA protective mechanism. Finally, pregnenolone evaluation in PIGA exposed cells revealed an increase in its synthesis, which was prevented by AMG pre-treatment. These findings indicate that these TSPO ligands reduce oxidative stress and pro-inflammatory enzymes in glial cells through the de novo synthesis of neurosteroids, suggesting that these compounds could be potential new therapeutic tools for the treatment of inflammatory-based neuropathologies with beneficial effects possibly comparable to steroids, but potentially avoiding the negative side effects of long-term therapies with steroid hormones

Management of patients with early-stage colon cancer: guidelines of the Italian Medical Oncology Association

About 75% of colorectal cancers are diagnosed as early stage, in which radical surgery is achievable. In the last decade, in Italy, the overall incidence of colorectal cancer has remained stable, while mortality gradually decreased, which is attributable to early diagnosis and improved medical, surgical and locoregional treatments. The Italian Medical Oncology Association formulated guidelines to manage early-stage colon cancer, including screening, diagnosis, treatment and follow-up, which we herein present