Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, we characterized EMT in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells simultaneously expressed mesenchymal and epithelial markers, but mesenchymal cells were highly enriched in CTCs. Serial CTC monitoring in 11 patients suggested an association of mesenchymal CTCs with disease progression. In an index patient, reversible shifts between these cell fates accompanied each cycle of response to therapy and disease progression. Mesenchymal CTCs occurred as both single cells and multicellular clusters, expressing known EMT regulators, including transforming growth factor (TGF)–β pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.

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Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition

Circulating Tumor Cell Clusters Are Oligoclonal Precursors of Breast Cancer Metastasis

https://www.cell.com/cell/pdf/S0092-8674(11)01369-9.pdf

EMT and Dissemination Precede Pancreatic Tumor Formation

Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. Elevated levels of serum IL-6 and TNF-α at the time of hospitalization are independent and significant predictors of clinical outcome in two cohorts of patients with COVID-19.

/pdf/an-inflammatory-cytokine-signature-predicts-covid-19-1koyptwi73.pdf

An inflammatory cytokine signature predicts COVID-19 severity and survival.

The success of anticancer therapy is usually limited by the development of drug resistance. Such acquired resistance is driven, in part, by intratumoural heterogeneity - that is, the phenotypic diversity of cancer cells co-inhabiting a single tumour mass. The introduction of the cancer stem cell (CSC) concept, which posits the presence of minor subpopulations of CSCs that are uniquely capable of seeding new tumours, has provided a framework for understanding one dimension of intratumoural heterogeneity. This concept, taken together with the identification of the epithelial-to-mesenchymal transition (EMT) programme as a critical regulator of the CSC phenotype, offers an opportunity to investigate the nature of intratumoural heterogeneity and a possible mechanistic basis for anticancer drug resistance. In fact, accumulating evidence indicates that conventional therapies often fail to eradicate carcinoma cells that have entered the CSC state via activation of the EMT programme, thereby permitting CSC-mediated clinical relapse. In this Review, we summarize our current understanding of the link between the EMT programme and the CSC state, and also discuss how this knowledge can contribute to improvements in clinical practice.

EMT, CSCs, and drug resistance: the mechanistic link and clinical implications

/pdf/education-the-phd-factory-45t9fs6vpf.pdf

Education: The PhD factory

A powerful gene-editing technology is the biggest game changer to hit biology since PCR. But with its huge potential come pressing concerns.

CRISPR, the disruptor

In a large trial, a cheap and widely available steroid cut deaths by one-third among patients critically ill with COVID-19. In a large trial, a cheap and widely available steroid cut deaths by one-third among patients critically ill with COVID-19.

Coronavirus breakthrough: dexamethasone is first drug shown to save lives.

Interdisciplinarity has become all the rage as scientists tackle climate change and other intractable issues. But there is still strong resistance to crossing borders.

/pdf/how-to-solve-the-world-s-biggest-problems-4v86jvhjsr.pdf

How to solve the world's biggest problems

Clinical trials are crumbling under modern economic and scientific pressures. Nature looks at ways they might be saved.

/pdf/translational-research-4-ways-to-fix-the-clinical-trial-m2ptn33lws.pdf

Heidi Ledford

Papers

Education: The PhD factory

CRISPR, the disruptor

Coronavirus breakthrough: dexamethasone is first drug shown to save lives.

How to solve the world's biggest problems

Translational research: 4 ways to fix the clinical trial