RESUMO
BACKGROUND: Acute-on-chronic liver failure (ACLF) mostly occurs when there is an acute insult to the liver in patients with pre-existing liver disease, and it is characterized by a high mortality rate. Various therapeutic approaches have been used thus far, with orthotopic liver transplantation being the only definitive cure. Clinical trials and meta-analyses have investigated the use of granulocyte colony-stimulating factor (G-CSF) to mobilize bone marrow-derived stem cells. Some studies have suggested that G-CSF may have a significant role in the management and survival of patients with ACLF. However, the results are conflicting, and the efficacy of G-CSF still needs to be confirmed. AIM: The aim was to assess the efficacy of G-CSF in patients with ACLF. METHODS: Electronic databases were searched until May 2023 for randomized controlled trials investigating the use of G-CSF in adult patients with ACLF. Outcome measures were the effects of G-CSF on overall survival, changes in liver disease severity scores, complications of cirrhosis, other G-CSF-related adverse effects, and all-cause mortality. The study's protocol has been registered with Prospero (CRD42023420273). RESULTS: Five double-blind randomized controlled trials involving a total of 421 participants met the inclusion criteria. The use of G-CSF demonstrated a significant effect on overall survival (HR 0.63, 95% CI 0.41 to 0.95, and I2 48%), leading to a decreased mortality (LogOR-0.97, 95% CI -1.57 to -0.37, and I2 37.6%) and improved Model for End-Stage Liver Disease (MELD) scores (SMD -0.87, 95% CI -1.62 to -0.13, and I2 87.3%). There was no correlation between the improvement of the Child-Pugh score and the use of G-CSF(SMD -2.47, 95% CI -5.78 to 0.83, and I2 98.1%). The incidence of complications of cirrhosis did not decrease significantly with G-CSF treatment (rate ratio 0.51, 95% CI 0.26 to 1.01, and I2 90%). A qualitative synthesis showed that the use of G-CSF is safe. CONCLUSIONS: The administration of G-CSF has demonstrated a positive impact on overall survival, liver function, and the MELD score. The presence of heterogeneity in the included studies prohibits conclusive recommendations.
RESUMO
BACKGROUND: It is well accepted that the bidirectional crosstalk between platelets and cancer cells promotes tumorigenesis and metastasis. In an early step, cancer cells trigger platelet granule and extracellular vesicle release that is needed to facilitate cancer cell survival in circulation. OBJECTIVES: To discover the early crosstalk of cancer cells and platelets. METHODS: Cancer cells were incubated with freshly isolated and stained human platelets. Confocal laser scanning microscopy and flow cytometry was used to visualize and to quantify platelet uptake and the membrane presence of CD42 on cancer cells. Dyngo4a was used to test if platelet uptake is a dynamin-dependent process. RESULTS: We found a dynamin-dependent uptake of platelets by cancer cells. This is followed by the recycling of the platelet-specific protein CD42a and its incorporation into cancer cells' plasma membrane, which is not a result of platelet RNA transfer by platelet-derived microparticles and exosomes. Time course of platelet uptake follows a sigmoid function revealing that 50% of the cancer cells are positive for platelets after approximately 38 min. Platelet uptake was observed for the tested cancerous cells (A549, MCF-7, and MV3) but not for the non-cancerous cell line 16HBE14o-. CONCLUSIONS: Our results demonstrate that cancer cells hijack platelets by phagocytosis and recycling of platelet membrane proteins. The uptake of platelets has additional advantages for cancer cells: access to the entire and undiluted platelet proteome, transcriptome, and secretome. These novel findings will allow further mechanistic elucidation and thus help us gain deeper insights into platelet-assisted hematogenous metastasis.