Myocarditis is characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function with a heterogeneous etiology. Both viral- and myosin-induced myocarditis experiment...
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Myocarditis is characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function with a heterogeneous etiology. Both viral- and myosin-induced myocarditis experimental models are used to mimic myocarditis in humans. Here, coxsackie virus B3-induced and non-virus-induced myocarditis models and data obtained in clinical studies were reviewed. Experimental murine myocarditis following immunization with α-myosin together with complete Freund adjuvant represents the classical immune-mediated model. T helper 1 (Th1) and Th2 pathways and important cytokines are involved in the autoimmunity of myocarditis, and the dynamic balance between Th17 and regulatory T cell seems to have an important role in the process of myocarditis. The purpose of this review is to summarize the existing understanding of the immunological mechanisms underlying myocarditis and exploring gaps in knowledge in both animal and human studies, since these mechanistic insights are a critical requirement for the development of novel therapeutic and vaccination strategies.
AIM: To investigate efficacy and safety of second-line treatment with irinotecan-loaded drug-eluting beads(DEBIRI) and cetuximab(DEBIRITUX) of unresectable colorectal liver ***: Patients with the following characteris...
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AIM: To investigate efficacy and safety of second-line treatment with irinotecan-loaded drug-eluting beads(DEBIRI) and cetuximab(DEBIRITUX) of unresectable colorectal liver ***: Patients with the following characteristics were included in the study: unresectable hepatic metastases from colorectal carcinoma(CRC-LM), progression after first line chemotherapy(any type of chemotherapeutic drug and combination was allowed), second line treatment(mandatory), which included for each patient(unregarding the KRas status) two cycles of DEBIRI(using 100-300 μm beads loaded with irinotecan at a total dose 200 mg) followed by 12 cycles of cetuximab that was administered weekly at a first dose of 400 mg/m2 and then 250 mg/m2; good performance status(0-2) and liver functionality(alanine aminotransferase and gamma-glutamyl transferase not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/m L). Data were collected retrospectively and included: tumor response(evaluated monthly for 6 mo then every 3 mo), overall response rate(ORR), KRas status, type and intensity of adverse events(G according to the Common Terminology Criteria for Adverse Events v3.0, CTCAE), overall survival(OS) and progression free survival(PFS).RESULTS: Forty consecutive cases of CRC hepatic metastases were included in the study. Median duration of DEBIRITUX was 4.4 mo(range, 4.0-6.5). Sixteen patients(40%) received the planned 2 cycles of DEBIRI and an average of 10 cetuximab cycles. ORR of the whole sample was 50%, in particular 4 patients were complete responders(10%) and 16(40%) partial responders. The most observed side effects(G2) were: post-embolization syndrome(30%), diarrhea(25%), skin rushes(38%) and asthenia(35%). The retrospective evaluation of KRas status(24 wild type, 16 mutated) showed that the group of patients with wild type KRas had ORR significantly higher than mutant KRas. Median follow-up was 29 mo(8-48 range); median PFS was 9.8 mo and OS was
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