Background: The increased bone marrow angiogenesis is involved in the progression of multiple myeloma (MM) with the underlying mechanism poorly understood. Cancer-released exosomes could play an important role in the pathological angiogenesis through exosomal microRNAs (miRs) delivery. It is reported that miR-29b played an important role in regulating the tumor angiogenesis. Methods: In this study, we explored the role of C6-ceramide (C6-cer, a Ceramide pathway activator) in the angiogenic effect of MM exosomes and its potential mechanism. MM cells (OPM2 and RPMI-8226) treated with C6-cer were studied for its effects on the endothelial cell (EC) functions. Results: Our results showed that exosomes released from MM cells treated by C6-cer (ExoC6-cer) significantly inhibited the proliferation, migration and tube formation of ECs. For mechanism studies, we found that the level of miR-29b was increased in ECs treated by ExoC6-cer, while mRNA and protein expressions of Akt3, PI3K and VEGFA were decreased in ECs, indicating the involvement of Akt pathway. Furthermore, downregulation of miR-29b by inhibitor administration could prevent the ExoC6-cer-induced cell proliferation, migration and angiogenesis of ECs, accompanied with the increased expressions of Akt3, PI3K and VEGFA. Conclusions: Collectively, our data suggest that ExoC6-cer-mediated miR-29b expression participates in the progression of MM through suppressing the proliferation, migration and angiogenesis of ECs by targeting Akt signal pathway.
Owing to the nature of acute illness and adverse effects derived from intensive chemotherapy, patients with hematological malignancies (HM) who are admitted to the Intensive Care Unit (ICU) often present with poor prognosis. However, with advances in life-sustaining therapies and close collaborations between hematologists and intensive care specialists, the prognosis for these patients has improved substantially. Many studies from different countries have examined the prognostic factors of these critically ill HM patients. However, there has not been an up-to-date review on this subject, and very few studies have focused on the prognosis of patients with HM admitted to the ICU in Asian countries. Herein, we aim to explore the current situation and prognostic factors in patients with HM admitted to ICU, mainly focusing on studies published in the last 10 years.
13 June 2023 in Clinical and Experimental Pharmacology and Physiology
Disease relapse is a major cause of treatment failure after allogeneic haematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). We retrospectively evaluated all patients (n = 145) with high-risk AML and MDS who underwent allo-HSCT between 2016 and 2022. Among them, 53 patients received maintenance therapy with azacitidine (AZA), and 10 of these patients received preemptive therapy. The rest of the 92 patients were in the control arm. The median follow-up time was 1215 days (103–3173 days). The median number of administered AZA cycles was 8. The 2-year relapse-free survival was 86.8% (46/53) in the AZA group compared with 76.1% (70/92) in the control group (P = 0.121). The 2-year overall survival in the AZA and control groups were 88.7% (47/53) and 82.6% (76/92), respectively (P = 0.326). Six patients (11.3%) in the AZA group experienced relapse, all of whom had a minimal residual disease (MRD)-positive status pre-HSCT. A total of 17 (32.1%) patients experienced grade 3–4 adverse events. In the preemptive therapy group, 70% (7/10) of the patients achieved complete remission after AZA treatment. AZA maintenance therapy following allo-HSCT is well tolerated and further follow-up and a larger group of patients will be necessary to confirm the potential to prevent relapse. The pre-transplant MRD status was identified as an important factor affecting the efficacy of AZA maintenance therapy.