1More than two centuries later, the aesthetic reflection of Idealism does not seem to have lost interest in philosophical debate at all. It is a multifaceted interest, which has partly ...historical-conceptual reasons, since it was post-Kantian philosophy that first posed the problem of defining art in systematic and cognitive terms, and partly more genuinely theoretical ones, for instance the contemporary declinations of a typically Idealistic theme such as the socio-historical determination o...
Literature plays a relevant role in Hegel’s philosophical discourse. On the one hand, literary references are often interwoven with his speculative argumentation, on the other hand, the Aesthetics ...regards poetry as the highest form of artistic expression, for it is able to represent the different ways of human action and to bring up their hidden ideal presuppositions. The aim of this paper is to show how the concept of action is crucial to the interpretation of literary phenomena in the Aesthetics, but assumes different configurations in relation to the historical transformation of the concept of subjectivity. To verify the specifically aesthetic import of concepts such as action and recognition, which originally belong to the ethical-political sphere, I will examine Hegel’s interpretation of the chivalric literature, which is present in various areas and with different functions in the structure of the Aesthetics, as a component of his theory of subjectivity. This topic has been little studied but offers an interesting perspective on some problematic points of Hegel’s theory: the controversial relation between the structural dimension of the concept of art and historical development of artistic forms, the apparently univocal paradigm of classic beauty, and the definition of artistic modernity.
Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients.
A review of clinical trials, retrospective ...studies and case reports was performed regarding molecular biomarkers with therapeutic implications.
wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge strategy. Antiangiogenic therapies improve survival in first- and second-line settings, irrespective of
status, while tyrosine kinase inhibitors (TKIs) remain promising in refractory mCRC. Promising results emerged from anti-HER2 drugs trials in HER2-positive mCRC. Target inhibitors were successful for
mutant mCRC patients, while immunotherapy was successful for microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) or DNA polymerase epsilon catalytic subunit (
) mutant patients. Data are still lacking on
, and TGF-β, which require further research.
Several molecular biomarkers have been identified for the tailored treatment of mCRC patients and multiple efforts are currently ongoing to increase the therapeutic options. In the era of precision medicine, molecular-biology-driven treatment is the key to impro patient selection and patient outcomes. Further research and large phase III trials are required to ameliorate the therapeutic management of these patients.
Rechallenge with EGFR inhibitors represents a promising strategy for patients with RAS wild type (WT) colorectal cancer (CRC) but definitive selection criteria are lacking. Recently, the RAS WT ...status on circulating tumor DNA (ct-DNA) emerged as a potential watershed for this strategy. Our study explored the liquid biopsy-driven cetuximab rechallenge in a RAS and BRAF WT selected population.
CRC patients with RAS and BRAF WT both on tumor tissue and on ct-DNA at baseline receiving rechallenge with cetuximab were eligible for our analysis. Ct-DNA was analyzed for RAS-BRAF mutations with pyro-sequencing and nucleotide sequencing assays. Real-time PCR and droplet digital PCR were performed to confirm the RAS-BRAF mutational status.
A total of 26 patients were included in our analysis. In the global population, RR was 25.0%, median overall survival (mOS) was 5.0 months, and median progression-free survival (mPFS) was 3.5 months. Previous response to anti-EGFR was associated with improved mPFS (5.0 vs. 2.0 months, HR: 0.26,
= 0.048); anti-EGFR free interval > 14 months and anti-EGFR free interval > 16 months were associated with improved mPFS (respectively 7.0 vs. 3.0 months, HR: 0.27,
= 0.013 and not reached vs. 3.0 months, HR: 0.20,
= 0.002) and with improved mOS (respectively 13.0 vs. 5.0 months, HR: 0.27,
= 0.013 and 13.0 vs. 5.0 months, HR: 0.20,
= 0.002). Previous lines >2 were correlated with improved mPFS (4.0 vs. 1.0 month, HR: 0.05,
= 0.041) and with improved mOS (7.0 vs. 1.0 month, HR: 0.045,
= 0.034). In a multiple logistic regression model, only the anti-EGFR free interval was confirmed to be a significant predictor for mOS and mPFS.
Liquid biopsy-driven cetuximab rechallenge was confirmed to be effective. The clinical outcome was consistent with available results from phase II studies. In addition to the molecular selection through the analysis of ct-DNA for RAS, the long anti-EGFR free interval is confirmed as a prospective selection criterion for this therapeutic option.
“The theory of art is its own history”. Thus writes Friedrich Schlegel in Dialogue on Poetry, defining aesthetics in a way that decidedly departs from Kant’s Critique of the Power of Judgment and ...prefigures Hegel’s position, although Hegel will almost always turn out to take a polemical stance toward the Romantics. In the few years between the end of the eighteenth century and the beginning of the nineteenth, there is a shift from an aesthetics of nature to an aesthetics of art, from an aest...
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