3D Cone Beam CT analysis of osteophytic neoformations in the temporomandibular joint

Aim: The aim is to show the usefulness of Cone Beam Computed Tomography (CBCT) in the study of the temporomandibular joint (TMJ) of patients with Rheumatoid Arthritis (RA), especially if by CT scans reveal the presence of osteophytic growths otherwise not visible with conventional radiographic techniques. Materials and Methods: Osteophyte is the medical term for a bone formation attempt to increase the articular surface of the load, it is the attempt to repair what the articulation performs to compensate for a bone defect or damage joint surfaces due to arthritis or trauma. Results: The examination CBCT allows accurate morphological analysis of articular surfaces in the three planes of space TMJ, not previously possible with traditional two-dimensional X-ray methods. The analysis highlights both the changes on surfaces such as cortical erosions, flattening, sclerosis, osteophytes and joint space narrowing, and changes in mineralization of bone considered. Conclusions: In Ra patients, the TMJ is commonly affected, but the diagnosis is often delayed due to lack of symptoms. In these cases, an CBCT provides the clinician with the advantage of highlighting condylar lesions as small scale and allows to establish appropriate therapy at an early stage, reducing complications for these patients

Tandem chemiluminescence-flow injection analysis for dimethoate determination

This work was supported by the Ministry of Education and Science of Spain (Project CTM2006-11991) and FEDER funds.Catalá Icardo, M.; López Paz, JL.; Choves Barón, C. (2010). Tandem chemiluminescence-flow injection analysis for dimethoate determination. Luminescence. 25:235-236. https://doi.org/10.1002/bio.1217S2352362

Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer)

Background: First-line chemotherapy regimens suitable for elderly advanced breast cancer patients are still not defined. Patients and methods: Women with stage III or IV breast cancer aged >_70 years were enrolled in a phase II study aimed to evaluate both activity and toxicity of weekly paclitaxel. Among 46 planned patients, at least 18 responses and not more than seven unacceptable toxic events are required for a favourable conclusion. Paclitaxel 80 mg/m2 was administered weekly for 3 weeks every 28 days. Results: Unacceptable toxicity occurred in seven out of 46 patients evaluated for toxicity [15.2%; exact 95% confidence interval (CI) 7.6% to 28.2%] and was represented by one case of febrile neutropenia, one case of severe allergic reaction and five cases of cardiac toxicity. Among 41 patients evaluated for response, a complete response occurred in two (4.9%) patients and a partial response in 20 (48.8%), with an overall response rate of 53.7% (exact 95% CI 38.7% to 67.9%). The median progression-free survival was 9.7 months (95% CI 8.5\u201318.7) and median survival was 35.8 months (95% CI 19\u2013not defined). Conclusions: Weekly paclitaxel is highly active in elderly advanced breast cancer patients. Data on cardiovascular complications, however, indicate the need for a careful monitoring of cardiac function before and during chemotherap

ps4 70 anti phosphatidylserine prothrombin antibodies and cardiovascular risk in a sle cohort of patients

Introduction Clinical activity of SLE may wax and wane, but persistent, active systemic inflammation leads to organ damage and rises morbidity and mortality. Early damage is mostly related to disease activity, whereas later damage, in particular atherosclerosis, infections and malignancies are usual complications of long-standing disease and treatment with immunosuppressive agents. One of the major late causes of death in SLE is thrombosis, in particular stroke and myocardial infarction due to CAD. In these patients, the increased cardiovascular morbidity is not fully explained by traditional risk factors and this may lead to under-recognition and under-treatment. Petri, et al. proposed an equation for cardiovascular disease risk in SLE, which combines classical parameters and disease activity markers. Other scores such as the GAPSS(Global AntiPhospholipid Syndrome Score) have been recently evaluated. The importance of aPL in thrombosis in general is well defined, as they constitute the culprit of the so-called anti-phospholipid syndrome(APS). Their role in sustaining the high risk of cardiovascular complications of SLE patients is under-debated. Objective To study the role of the anti-phosphatidylserine/prothrombin(aPS/PT) antibodies, included in the GAPSS score, in contributing to the thrombotic risk of SLE patients. Methods We enrolled 172 patients from Ospedale San Raffaele. 132 patients with SLE(111/132, 84% without secondary APS, SAPS, and 21/132, 16% with SAPS), 19 with primary APS(PAPS) and 21 healthy controls. Each recruited patient was tested for aPS/PT IgG and IgM through ELISA by INOVA Diagnostic, Inc. San Diego, CA USA. Results 36/111 (32.4%) SLE without APS, 15/21 (71.4%) SAPS, 13/19 (68.4%) PAPS and 3/21 (14.3%) healthy donors were aPS/PT+. aPS/PT+SLE patients had a higher cardiovascular risk according to the Petri's score, when compared to aPS/PT-patients, irrespectively of a positive or negative history of overt APS(Mean ±SD Petri' score=20.8±18.1, 14.0±12.8 and 23.8±22.5, 11.6±9.3 respectively, p 10 had also higher prevalence of pregnancy complications. Conclusion aPS/PT antibodies are associated with a high risk of thrombosis and CAD in SLE. aPS/PT assays should be routinely introduced in the management of these patients

uPAR controls vasculogenic mimicry ability expressed by drug-resistant melanoma cells.

Malignant melanoma is a highly aggressive skin cancer characterized by an elevated grade of tumor cell plasticity. Such plasticity allows adaptation of melanoma cells to different hostile conditions and guarantees tumor survival and disease progression, including aggressive features such as drug resistance. Indeed, almost 50% of melanoma rapidly develop resistance to the BRAF(V600E) inhibitor vemurafenib, with fast tumor dissemination, a devastating consequence for patients’ outcomes. Vasculogenic mimicry (VM), the ability of cancer cells to organize themselves in perfused vascular-like channels, might sustain tumor spread by providing vemurafenib-resistant cancer cells with supplementary ways to enter into circulation and disseminate. Thus, this research aims to determine if vemurafenib resistance goes with the acquisition of VM ability by aggressive melanoma cells, and identify a driving molecule for both vemurafenib resistance and VM. We used two independent experimental models of drug-resistant melanoma cells, the first one represented by a chronic adaptation of melanoma cells to extracellular acidosis, known to drive a particularly aggressive and vemurafenib-resistant phenotype, the second one generated with chronic vemurafenib exposure. By performing in vitro tube formation assay and evaluating the expression levels of the VM markers EphA2 and VE-cadherin by Western blotting and flow cytometer analyses, we demonstrated that vemurafenib-resistant cells obtained by both models are characterized by an increased ability to perform VM. Moreover, by exploiting the CRISPR-Cas9 technique and using the urokinase plasminogen activator receptor (uPAR) inhibitor M25, we identified uPAR as a driver of VM expressed by vemurafenib-resistant melanoma cells. Thus, uPAR targeting may be successfully leveraged as a new complementary therapy to inhibit VM in drug-resistant melanoma patients, to counteract the rapid progression and dissemination of the disease

GDF5 regulates TGFß-dependent angiogenesis in breast carcinoma MCF-7 cells: in vitro and in vivo control by anti-TGFß peptides

BACKGROUND: TGFß overproduction in cancer cells is one of the main characteristics of late tumor progression being implicated in metastasis, tumor growth, angiogenesis and immune response. We investigated the therapeutic efficacy of anti-TGFß peptides in the control of angiogenesis elicited by conditional over-expression of TGFß. METHODS: We have inserted in human MCF7 mammary-cancer cells a mutated TGFß gene in a tetracycline-repressible vector to obtain conditional expression of mature TGFß upon transient transfection, evaluated the signaling pathways involved in TGFß-dependent endothelial cells activation and the efficacy of anti-TGFß peptides in the control of MCF7-TGFß-dependent angiogenesis. RESULTS: TGFß over-expression induced in MCF7 several markers of the epithelial-to-mesenchymal transition. Conditioned-medium of TGFß-transfected MCF7 stimulated angiogenesis in vivo and in vitro by subsequent activation of SMAD2/3 and SMAD1/5 signaling in endothelial cells, as well as SMAD4 nuclear translocation, resulting in over-expression of the pro-angiogenic growth and differentiation factor-5 (GDF5). Inhibition or silencing of GDF5 in TGFß-stimulated EC resulted in impairment of GDF5 expression and of TGFß-dependent urokinase-plasminogen activator receptor (uPAR) overproduction, leading to angiogenesis impairment. Two different TGFß antagonist peptides inhibited all the angiogenesis-related properties elicited in EC by exogenous and conditionally-expressed TGFß in vivo and in vitro, including SMAD1/5 phosphorylation, SMAD4 nuclear translocation, GDF5 and uPAR overexpression. Antagonist peptides and anti-GDF5 antibodies efficiently inhibited in vitro and in vivo angiogenesis. CONCLUSIONS: TGFß produced by breast cancer cells induces in endothelial cells expression of GDF5, which in turn stimulates angiogenesis both in vitro and in vivo. Angiogenesis activation is rapid and the involved mechanism is totally opposed to the old and controversial dogma about the AKL5/ALK1 balance. The GDF-dependent pro-angiogenic effects of TGFß are controlled by anti-TGFß peptides and anti-GDF5 antibodies, providing a basis to develop targeted clinical studies