Inter-modelling: From Theory to Practice

Proocedings of: ACM/IEEE 13 th International Conference on Model Driven Engineering Languages and Systems. Oslo, Norway, October 3-8, 2010.We define inter-modelling as the activity of building models that describe how modelling languages should be related. This includes many common activities in Model Driven Engineering, like the specification of model-to-model transformations, the definition of model matching and model traceability constraints, the development of inter-model consistency maintainers and exogenous model management operators. Recently, we proposed a formal approach to specify the allowed and forbidden relations between two modelling languages by means of bidirectional declarative patterns. Such specifications were used to generate graph rewriting rules able to enforce the relations in (forward and backward) model-to-model transformation scenarios. In this paper we extend the usage of patterns for two further inter-modelling scenarios &- model matching and model traceability &- and report on an EMF-based tool implementing them. The tool allows a high-level analysis of specifications based on the theory developed so far, as well as manipulation of traces by compilation of patterns into the Epsilon Object Language.Work funded by the Spanish Ministry of Science (project TIN2008-02081 and grants JC2009-00015, PR2009-0019), the R&D programme of the Madrid Region (project S2009/TIC-1650), the European Commission’s 7th Framework programme (grant #248864 (MADES)), and the Engineering and Physical Sciences Research Council (EPSRC) (grant EP/E034853/1).Publicad

The role of the cell adhesion molecules (integrins/cadherins) in prostate cancer

During prostate carcinogenesis the cellular adhesion molecules, i.e.; integrins and cadherins mediate aberrant interactions between glandular epithelial cells and the extracellular matrix. Several integrin α subunits are downregulated, while β subunits are up-regulated. The expression of several cadherins and catenins has specific prognostic value. There is an association between the expression of the E-cadherin/catenin complex and high grade prostate cancer. Clinical trials evaluating the efficacy of integrin antagonists are ongoing with promising results. In this article we update the role of integrins and cadherins in prostate carcinogenesis and evaluate the therapeutic potential of their manipulation

The role of the cell adhesion molecules (integrins / cadherins) in prostate cancer

During prostate carcinogenesis the cellular adhesion molecules, i.e.; integrins and cadherins mediate aberrant interactions between glandular epithelial cells and the extracellular matrix. Several integrin α subunits are down-regulated, while β subunits are up-regulated. The expression of several cadherins and catenins has specific prognostic value. There is an association between the expression of the E-cadherin/catenin complex and high grade prostate cancer. Clinical trials evaluating the efficacy of integrin antagonists are ongoing with promising results. In this article we update the role of integrins and cadherins in prostate carcinogenesis and evaluate the therapeutic potential of their manipulation

Integrin expression in correlation to clinicopathological features and prognosis of prostate cancer: A systematic review and meta-analysis

Background: The prompt identification of patients with poor prognosis is essential in order to improve the treatment outcomes in prostate cancer (CaP); as a novel approach, several molecular markers, including integrins, have been discussed as prognostic biomarkers. Our aim was to comprehensively examine aberrant expression of integrins in correlation with clinicopathological features and prognosis in CaP by synthesizing all available evidence, in a systematic review and meta-analysis. Methods: A systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Scientific literature databases (Pubmed, Embase, and Scopus) were systematically searched until May 10, 2020. Random-effects (DerSimonian-Laird) models were used to estimate pooled odds ratios (ORs) for cross-sectional correlations with clinicopathological characteristics and relative risks for longitudinal associations with prognosis. Results: Fourteen studies were included with a total number of 3,194 CaP cases examined (13 cross-sectional and four longitudinal cohort study arms). Correlation of low expression of α6 (pooled OR = 0.10, 95% confidence interval [CI]: 0.04–0.28, P < 0.001) and β1 (pooled OR = 0.45; 95% CI: 0.21–1.00, P = 0.049) integrin with high Gleason score was noted. A borderline trend between reduced expression of α6 integrin and an advanced clinical stage of CaP (pooled OR = 0.48; 95% CI: 0.22-1.03, P = 0.06) was observed. No associations with biochemical recurrence and survival were documented. Conclusions: Evidence on the association of low expression of integrins α6 and β1 and more advanced CaP exist, whereas significant results on survival were not documented; further studies are warranted. © 2021 Elsevier Inc

The role of the cell adhesion molecules (integrins/cadherins) in prostate cancer

During prostate carcinogenesis the cellular adhesion molecules, i.e.; integrins and cadherins mediate aberrant interactions between glandular epithelial cells and the extracellular matrix. Several integrin α subunits are downregulated, while β subunits are up-regulated. The expression of several cadherins and catenins has specific prognostic value. There is an association between the expression of the E-cadherin/catenin complex and high grade prostate cancer. Clinical trials evaluating the efficacy of integrin antagonists are ongoing with promising results. In this article we update the role of integrins and cadherins in prostate carcinogenesis and evaluate the therapeutic potential of their manipulation

Expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin in localized prostate cancer

Objective: To explore the correlation between the expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin in prostate cancer (PCa) and its clinicopathological data including tumor grade and clinical stage. Methods: The expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin was examined in 157 cases of PCa and adjacent normal prostatic tissue by immunohistochemical assay, and the correlation with clinicopathological features was analyzed. Results: Expressions of α5-integrin, α7-integrin, and Ε-cadherin in PCa were lower than those in normal prostatic tissues (P<0.05). N-cadherin expression was higher in cancer prostatic tissue than in normal prostatic tissues (P<0.05). The reduced expression of α5-integrin, α7-integrin, and Ε-cadherin was related to Gleason score, pathological stage, lymph node metastasis, and prostate-specific antigen level, but it was not associated with positive surgical margins and patient age. The increased expression of N-cadherin was related to Gleason score, pathological stage, lymph node metastasis, and prostate-specific antigen level, but not to age and positive surgical margins. The expression of E-cadherin was highly negatively correlated with that of N-cadherin and also positively correlated with that of α5-integrin and α7-integrin. Conclusion: The reduced expression of α5-integrin, α7-integrin, and Ε-cadherin and abnormal expression of N-cadherin play an important role in the occurrence and development of PCa. The results indicate that these have potential values in the diagnosis and are predictable indices in the proliferation of PCa. © 2016 Elsevier Inc

Risk for Venous Thromboembolic Events in Patients With Advanced Urinary Tract Cancer Treated With First-Line Chemotherapy

We identified the incidence and risk factors of venous thromboembolism in 335 chemotherapy-treated patients with urothelial cancer. The Khorana risk score did not accurately predict risk for thromboembolic events; on the contrary, history of vascular events was associated with a 3-fold increase of this risk. The role of prophylaxis in this group should be further studied. © 2020 Elsevier Inc. Background: Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer-associated thrombosis have been proposed. However, advanced urinary tract cancer (aUTC) was not adequately represented in these models. We studied the incidence of VTEs, the risk factors, and the applicability of recently described RAMs. Patients and Methods: Data from 335 patients with aUTC treated with chemotherapy between April 1995 and September 2015 in a single institution were analyzed. Results: A total of 95.2% received platinum-based first-line chemotherapy. Twenty-nine patients (8.7%) experienced VTEs. The 6-, 12-, and 24-month VTE incidence was 7.4% (95% confidence interval [CI], 4.8-10.6), 8.1% (95% CI, 5.4-11.5) and 9.4% (95% CI, 6.4-13.1), respectively. No significant association of VTE incidence with the Khorana risk score was observed. History of vascular event (VTE and/or arterial thromboembolic event) was significantly associated with the development of VTE. Patients with such history had a 6-, 12-, and 24-month VTE incidence of 16.2% (95% CI, 6.6-29.7), 19.2% (95% CI, 8.4-33.3), and 25.2% (95% CI, 12.5-40.1) compared to 6.2% (95% CI, 3.7-9.4), 6.6% (95% CI, 4.1-10), and 7.1% (95% CI, 4.4-10.6) of those who did not. The discriminatory ability of this factor adjusted for leucocyte count, sex, Eastern Cooperative Oncology Group performance status, and type of chemotherapy reached 0.79 (95% CI, 0.71-0.87) compared to the 0.58 (95% CI, 0.49-0.66) for the Khorana risk score. Conclusion: Development of tumor-specific algorithms for the risk of VTEs is advisable. Patients with aUTC and a history of vascular events are at high risk for VTE development, and prophylaxis should be prospectively studied in this group. © 2020 Elsevier Inc

Domain-specific metamodelling languages for software language engineering

Domain-specific languages are constructed to provide modelling capabilities tailored to a specific domain. Sometimes, languages are developed many times, typically to support application in a new context. In doing so, recurring patterns and commonalities as well as variations across the evolving set of languages can be identified. This paper introduces the concept of a domain-specific metamodelling language, which codifies such commonalities and provides concepts and logic for expressing the variations. The challenges and difficulties of using domain-specific metamodelling languages are identified. We illustrate the concept with examples from different domains