Erratum to: Integrated molecular dissection of the epidermal growth factor receptor (EGFR) oncogenic pathway to predict response to EGFR-targeted monoclonal antibodies in metastatic colorectal cancer

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Sensitivity to Entrectinib Associated with a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer

In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models. We identified abnormal expression of the TRKA protein in tumor and liver metastases of a CRC patient refractory to standard therapy. Molecular characterization unveiled a novel LMNA-NTRK1 rearrangement within chromosome 1 with oncogenic potential, and the patient was treated with the pan-TRK inhibitor entrectinib, achieving partial response with decrease in hepatic target lesions from 6.8 and 8.2cm in longest diameter to 4.7 and 4.3cm, respectively. To our knowledge, this is the first clinical evidence of efficacy for therapeutic inhibition of TRKA in a solid tumor, illuminating a genomic-driven strategy to identify CRCs reliant on this oncogene to be clinically targeted with entrectinib

Trapeziometacarpal osteoarthritis: pyrocarbon interposition implants

Purpose: the aim of this study was to evaluate the effectiveness of interposition arthroplasty of the trapeziometacarpal (TMC) joint with pyrolitic carbon implants for the treatment of TMC osteoarthritis. Methods: we evaluated two groups of patients surgically treated for TMC osteoarthritis: group 1 (34 patients - 36 TMC joints) treated with PyroDisk implantation and group 2 (25 patients - 25 TMC joints) treated with the Pyrocardan implant. All these patients were clinically evaluated at follow-up using the DASH score, Mayo Wrist score and VAS pain score. Results: the mean follow-up was 42 months in group 1 and 12 months in group 2. Both groups showed good clinical outcomes in terms of pain relief, range of motion, and pinch and grasp strength. Revision surgery was needed in only one case in group 1 (2.8%) and in three cases (12%) in group 2. Conclusions: prosthetic replacement of the TMC joint was found to be a good solution for low-demand patients. However, the PyroDisk could be a good solution in selected patients (Eaton stage I-III, non-subluxated joint): it provides good pain relief, good range of motion, good pinch and grasp strength, and stable results at more than three-years of follow-up. Level of evidence: Level IV, therapeutic case series

Long-term effect of pioglitazone vs glimepiride on lipoprotein oxidation in patients with type 2 diabetes: a prospective randomized study

AIMS: Type 2 diabetes (DM2) is associated to oxidative modifications of high-density lipoproteins (HDL), which can interfere with their function. Pioglitazone has proved effective in raising HDL cholesterol (HDL-C) and lowering small dense low-density lipoprotein (LDL), but no clinical studies have examined its effect on lipoprotein oxidation in patients with DM2. METHODS: We assessed the effect of pioglitazone vs glimepiride after 1 year on HDL oxidation, expressed as relative abundance of peptides containing Met112O in ApoA-I (oxApoA-I) estimated by mass spectrometry (MALDI/TOF/TOF), in 95 patients with DM2. The oxLDL and AGE were quantified by ELISA. RESULTS: Patients receiving pioglitazone showed a significant increase in the concentration of ApoA-I (\u394\u2009=\u20097.2\u2009\ub1\u200914.8 mg/dL, p\u2009<\u20090.02) and a reduction in oxApoA-I (\u394\u2009=\u2009-\u20091.0\u2009\ub1\u20092.6%, p\u2009<\u20090.02); this reduction was not significantly different from glimepiride. oxLDL showed a slight, but not significant increase in both treatment groups. Regression analysis showed a correlation between \u394oxApoA-I and \u394AGE (r\u2009=\u20090.30; p\u2009=\u20090.007) in all patients, while both of these parameters were unrelated to changes in HbA1c, HDL-C, duration of illness, or use of statins. CONCLUSIONS: Long-term treatment with pioglitazone was effective in reducing the oxidation of HDL, but not LDL in patients with DM2, while glimepiride didn't. This finding seems to be associated to the change of glyco-oxidation status, not to any improvement in glycemic control or lipid profile. TRIAL REGISTRATION: NCT00700856, ClinicalTrials.gov Registered June 18, 2008

«Storia dell'arte» in tempo reale. Anticipazioni e ricerche in corso, affacci sull'attualità, scoperte, nuove letture 2021-2022

In questa pubblicazione antologica sono raccolti gli articoli – dedicati a ricerche in corso, mostre, scoperte e riscoperte – pubblicati dall’aprile 2021 all’aprile 2022 nel sito web "Storia dell’arte" in tempo reale