Unravelling the biological and clinical challenges of circulating tumour cells in epithelial ovarian carcinoma.

Epithelial ovarian carcinoma (EOC) is the eighth most common cancer in women and the leading cause of gynaecological cancer death, predominantly due to the absence of effective screening tools, advanced stage at diagnosis, and high rates of recurrence. Circulating tumour cells (CTCs), are a rare subset of tumour cells that disseminate from a tumour and migrate into the circulation, play a pivotal role in the metastatic cascade, and therefore hold promise as biomarkers for disease monitoring and prognostication. Exploring CTCs from liquid biopsies is an appealing approach for research and clinical practice, given it is minimally invasive, facilitates serial sampling and enables the capture of the entire spectrum of cancer cells circulating in the blood. The prognostic utility of CTC enumeration has been FDA-approved for clinical use in metastatic breast, prostate, and colorectal cancers. However, the unique biology of EOC, discussed herein, compounds the detection and characterisation complexities already inherent in CTC research, consequently hindering progress towards clinical applications. The aim of this review is to provide an overview of both the biological and clinical challenges encountered in harnessing the power of CTCs in EOC.

A comparative study of circulating tumor cell isolation and enumeration technologies in lung cancer.

Circulating tumor cells (CTCs) have potential as diagnostic, prognostic, and predictive biomarkers in solid tumors. Despite Food and Drug Administration (FDA) approval of CTC devices in various cancers, the rarity and heterogeneity of CTCs in lung cancer make them technically challenging to isolate and analyze, hindering their clinical integration. Establishing a consensus through comparative analysis of different CTC systems is warranted. This study aimed to evaluate seven different CTC enrichment methods across five technologies using a standardized spike-in protocol: the CellMag™ (EpCAM-dependent enrichment), EasySep™ and RosetteSep™ (blood cell depletion), and the Parsortix® PR1 and the new design Parsortix® Prototype (PP) (size- and deformability-based enrichment). The Parsortix® systems were also evaluated for any differences in recovery rates between cell harvest versus in-cassette staining. Healthy donor blood (5 mL) was spiked with 100 fluorescently labeled EpCAMhigh H1975 cells, processed through each system, and the isolation efficiency was calculated. The CellMag™ had the highest recovery rate (70 ± 14%), followed by Parsortix® PR1 in-cassette staining, while the EasySep™ had the lowest recovery (18 ± 8%). Additional spike-in experiments were performed with EpCAMmoderate A549 and EpCAMlow H1299 cells using the CellMag™ and Parsortix® PR1 in-cassette staining. The recovery rate of CellMag™ significantly reduced to 35 ± 14% with A549 cells and 1 ± 1% with H1299 cells. However, the Parsortix® PR1 in-cassette staining showed cell phenotype-independent and consistent recovery rates among all lung cancer cell lines: H1975 (49 ± 2%), A549 (47 ± 10%), and H1299 (52 ± 10%). Furthermore, we demonstrated that the Parsortix® PR1 in-cassette staining method is capable of isolating heterogeneous single CTCs and cell clusters from patient samples. The Parsortix® PR1 in-cassette staining, capable of isolating different phenotypes of CTCs as either single cells or cell clusters with consistent recovery rates, is considered optimal for CTC enrichment for lung cancer, albeit needing further optimization and validation.

Negative Regulation of Innate Immune Signaling by Components of the Button Mushroom Agaricus bisporus.

SCOPE: Mushrooms are valued as an edible and medical resource for millennia. As macrofungi, they possess conserved molecular components recognized by innate immune cells like macrophages, yet unlike pathogenic fungi, they do not trigger the immune system in the same way. That these well-tolerated foods both avoid immuno-surveillance and have positive health benefits, highlights the dearth of information on the interactions of mushroom-derived products with the immune system. METHODS AND RESULTS: Using powders produced from the common white button mushroom, Agaricus bisporus, it is observed that pre-treatment of mouse and human macrophages with mushroom powders attenuates innate immune signaling triggered by microbial ligands like LPS and  ß-glucans, including NFκB activation and pro-inflammatory cytokine production. This effect of mushroom powders is observed at lower doses of TLR ligands, suggesting a model of competitive inhibition whereby mushroom compounds bind and occupy innate immune receptors, precluding activation by microbial stimuli. This effect is preserved following simulated digestion of the powders. Moreover, in vivo delivery of mushroom powders attenuates the development of colitis in a DSS-mouse model. CONCLUSION: This data highlights an important anti-inflammatory role for powdered A. bisporus mushrooms, which can be further utilized to develop complementary approaches to modulate chronic inflammation and disease.