Search

Background: The human placenta extrudes a variety of extracellular vesicles (EVs) into the maternal blood daily. These vesicles may be crucial to the adaptation of the maternal cardiovascular and immune systems to pregnancy. Quantifying the EVs that are released in early gestation is important to our understanding of how placental EVs may contribute to the regulation of maternal physiology.Methods: EVs were isolated from first trimester placental explants and separated into micro- and nano-vesicles by differential centrifugation. The numbers of each type of EVs extruded from each milligram of placentae between gestational weeks 8 and 12 was determined by Nanoparticle Tracking Analysis. The total protein or DNA content of the vesicles was determined by BCA assay or Qubit® 2.0.Results: Neither the number of micro- nor nano-EVs/mg explant (n = 49), nor the total protein (n = 19) and DNA content (n = 29) of these EVs changed significantly between 8 and 12 weeks of gestation. When the increasing placental weight with gestation was accounted for, the daily number of placental EVs extruded into the maternal blood increased by more than 100 fold between 8 and 12 weeks (micro-EVs 6.23 X 1014 and nano-EVs 1.84 X 1014 at 12 weeks, p = 0.0003).Discussion: Constant production of micro- and nano-EVs per-milligram placenta, regardless of gestational age, and the increased daily burden of EVs across gestational age indicate these EVs have the potential to regulate maternal physiology from early pregnancy. Since total EV protein content, like EV numbers was, constant, this is a potentially reliable surrogate for quantifying EVs. [ABSTRACT FROM AUTHOR]

Precision oncology guided by genomic research has an increasingly important role in the care of people with cancer. However, substantial inequities remain in cancer outcomes of Indigenous peoples, including Indigenous Māori in Aotearoa New Zealand (New Zealand). These inequities will be perpetuated unless deliberate steps are taken to include Indigenous peoples in all parts of cancer research-as research participants, in research leadership, and in research governance. This approach is especially important when there have been historical breaches of trust that have discouraged their participation in health research. This Personal View describes a precision oncology research roadmap for neuroendocrine tumour research, which seeks to reflect the values of New Zealand's Indigenous Māori people. This roadmap includes facilitating ongoing dialogue, Māori leadership, reciprocity, agreed kawa (guiding principles), tikanga (cultural protocols), and honest monitoring of what is and what is not being achieved. We challenge cancer researchers worldwide to generate locally appropriate roadmaps that honestly assess their practices to benefit Indigenous people internationally. [ABSTRACT FROM AUTHOR]

Summary: The extracellular matrix (ECM) can induce chemotherapy resistance via AKT-mediated inhibition of apoptosis. Here, we show that loss of the ECM protein TGFBI (transforming growth factor beta induced) is sufficient to induce specific resistance to paclitaxel and mitotic spindle abnormalities in ovarian cancer cells. Paclitaxel-resistant cells treated with recombinant TGFBI protein show integrin-dependent restoration of paclitaxel sensitivity via FAK- and Rho-dependent stabilization of microtubules. Immunohistochemical staining for TGFBI in paclitaxel-treated ovarian cancers from a prospective clinical trial showed that morphological changes of paclitaxel-induced cytotoxicity were restricted to areas of strong expression of TGFBI. These data show that ECM can mediate taxane sensitivity by modulating microtubule stability. [Copyright &y& Elsevier]

[Display omitted] • Polystyrene microtracks were patterned over a 100 mm diameter growth surface. • MDA-MB-231 cells increased alignment, aspect ratio and migration with microtracks. • Microtrack patterning increased extracellular vesicle production. Extracellular vesicles (EVs) are micro and nanoscale packages that circulate in all bodily fluids and play an important role in intercellular communication by shuttling biomolecules to nearby and distant cells. However, producing sufficient amounts of EVs for many types of in vitro studies using standard culture methods can be challenging, and despite the success of some bioreactors in increasing EV-production, it is still largely unknown how individual culture conditions can alter the production and content of EVs. In this study, we demonstrate a simple and inexpensive micropatterning technique that can be used to produce polystyrene microtracks over a 100 mm diameter growth surface area. We then demonstrate that these microtracks can play a significant role in increasing EV production using a triple-negative breast cancer cell line (MDA-MB-231) and that these changes in EV production correlate with increases in cellular aspect ratio, alignment of the cells' long axes to the microtracks, and single-cell migration rates. These findings have implications in both biomanufacturing of EVs and potentially in enhancing the biomimicry of EVs produced in vitro. [ABSTRACT FROM AUTHOR]