Search Results (3)

Gynecological malignancies (ovarian, endometrial, and cervical cancers), including disseminated intravascular coagulation (DIC), often provoke systemic coagulopathy. In recent years, tumor-derived, tissue factor–positive microparticles (TF⁺ MPs) have emerged as potent drivers of cancer-associated thrombosis and possibly DIC. These small (0.1–1 µm) membrane vesicles bud from cancer cell surfaces and carry procoagulant factors (phosphatidylserine and TF) on their surface. We review how TF⁺ MPs are generated by tumor cells and amplify the extrinsic coagulation cascade, potentially triggering DIC in patients with advanced gynecologic cancers. Clinical studies have linked el evated TF⁺ MP levels and activity to venous thromboembolism (VTE) in cancer, and small case series suggest dramatically high MP–TF activity in cancer-related DIC. We summarize evidence that TF⁺ MPs from ovarian tumors carry exceptionally high TF procoagulant activity (median ~80 pg/mL), and nearly all patients with cancer-associated VTE or DIC have MP–TF levels above normal. This review discusses diagnostic implications (e.g., measuring MP–TF activity as a biomarker) and treatment strategies (through the reduction in tumors, anticoagulation, and experimental TF inhibitors) in this setting. We also identify gaps in knowledge (standardized MP assays, prospective studies) and propose future directions (targeting MP formation or TF signaling). Two summary tables highlight recent studies of TF⁺ MPs in gynecologic cancer and their clinical outcomes. Illustrative figures depict the TF⁺ MP-triggered coagulation cascade and a conceptual framework for clinical management. Understanding TF⁺ MPs in gynecological cancer could improve the prediction and management of DIC and related thromboses. Full article

The Evate deposit is a Neoproterozoic (~590 Ma) magnetite-apatite-carbonate body emplaced parallel to foliation of the Monapo granulite complex in NE Mozambique. A complicated history of the deposit is recorded in apatite textures visualized in cathodoluminescence (CL) images. In spite of different solid and fluid inclusions, mineral assemblages, and the CL textures, electron probe microanalyses indicate relatively consistent apatite compositions corresponding to fluorapatite (X_F = 0.51–0.73, X_OH = 0.21–0.47, X_Cl = 0.02–0.06) with limited belovite- and cesanite-type substitutions. Laser ablation inductively coupled plasma mass spectrometric analyses show that apatites from unaltered magnetite-forsterite-spinel ores are depleted in Y, REE, Ba, and Sr compared to apatites from carbonate-anhydrite ores. Hydrothermally overprinted apatites with complex patchy domain CL textures are enriched in Y-REE in greenish-grey zones, Fe-U-Th in blue zones, and Mn-Sr-Ba in brown domains. Observed CL-emissions in the Evate apatites result from very subtle variations in REE, Mn, and U contents controlled by the variability of redox conditions. The decreased Th:U ratio in the hydrothermally overprinted apatites reflects the oxidation and partial removal of U⁴⁺ from the apatite structure during the interaction with oxidizing aqueous fluids capable of transporting U⁶⁺. Flat, LREE (La-Sm)-enriched chondrite-normalized patterns with Eu/Eu* = 0.7–1.4 and Ce/Ce* = 0.9–1.5, together with concentrations of diagnostic trace elements (Sr, Mn, Y, REE) are consistent with apatites from magmatic carbonatites and phoscorites. This study corroborates that the Evate deposit is a post-collisional orogenic carbonatite genetically linked with mafic plutonic rocks intruding the Monapo granulite complex after granulite-facies metamorphism, and later overprinted by intensive hydrothermalism. The Evate apatite is peculiar in retaining its pristine magmatic signature despite the extensive hydrothermal-metasomatic alteration accompanied by dissolution-reprecipitation. Full article

Immunotherapy can potentially treat cancers on a patient-dependent manner. Most of the efforts expended on anticancer vaccination parallel the efforts expended on prototypical immunization in infectious diseases. In this study, we designed and synthesized pH-responsive extracellular vesicles (EVs) coupled with hyaluronic acid (HA), 3-(diethylamino)propylamine (DEAP), monophosphoryl lipid A (MPLA), and mucin 1 peptide (MUC1), referred to as HDEA@EVAT. HDEA@EVAT potentiated the differentiation and maturation of monocytes into dendritic cells (DCs) and the priming of CD8⁺ T-cells for cancer therapy. MPLA and HA enabled HDEA@EVAT to interact with the toll-like receptor 4 and the CD44 receptor on DCs, followed by endosomal escape, owing to the protonation of pH-sensitive DEAP on the EV in conjunction with MUC1 release. The MUC1 was then processed and presented to DCs to activate CD8⁺ T-cells for additional anticancer-related immune reactions. Our findings support the anticancer vaccine activity by which HDEA@EVAT expedites the interaction between DCs and CD8⁺ T-cells by inducing DC-targeted maturation and by presenting the cancer-associated peptide MUC1. Full article