Cancer cells can divert metabolites into anabolic pathways to support their rapid proliferation and to accumulate the cellular building blocks required for tumor growth. However, the specific bioenergetic profile of invasive and metastatic cancer cells is unknown. Here we report that migratory/invasive cancer cells specifically favor mitochondrial respiration and increased ATP production. Invasive cancer cells use transcription co-activator, PGC-1α to enhance oxidative phosphorylation, mitochondrial biogenesis and oxygen consumption rate. Clinical analysis of human invasive breast cancers revealed a strong correlation between PGC-1α expression in invasive cancer cells and formation of distant metastases. Silencing of PGC-1α in cancer cells suspended their invasive potential and attenuated metastasis without affecting proliferation, primary tumor growth or epithelial-to-mesenchymal (EMT) program. While inherent genetics of cancer cells determine the transcriptome framework required for invasion and metastasis, mitochondrial biogenesis and respiration induced by PGC-1α is also essential for functional motility of cancer cells and metastasis.

<b><i>Background:</i></b> Critically ill patients with COVID-19 may develop multiple organ dysfunction syndrome, including acute kidney injury (AKI). We report the incidence, risk factors, associations, and outcomes of AKI and renal replacement therapy (RRT) in critically ill COVID-19 patients. <b><i>Methods:</i></b> We performed a retrospective cohort study of adult patients with COVID-19 diagnosis admitted to the intensive care unit (ICU) between March 2020 and May 2020. Multivariable logistic regression analysis was applied to identify risk factors for the development of AKI and use of RRT. The primary outcome was 60-day mortality after ICU admission. <b><i>Results:</i></b> 101 (50.2%) patients developed AKI (72% on the first day of invasive mechanical ventilation [IMV]), and thirty-four (17%) required RRT. Risk factors for AKI included higher baseline Cr (OR 2.50 [1.33–4.69], <i>p</i> = 0.005), diuretic use (OR 4.14 [1.27–13.49], <i>p</i> = 0.019), and IMV (OR 7.60 [1.37–42.05], <i>p</i> = 0.020). A higher C-reactive protein level was an additional risk factor for RRT (OR 2.12 [1.16–4.33], <i>p</i> = 0.023). Overall 60-day mortality was 14.4% {23.8% (<i>n</i> = 24) in the AKI group versus 5% (<i>n</i> = 5) in the non-AKI group (HR 2.79 [1.04–7.49], <i>p</i> = 0.040); and 35.3% (<i>n</i> = 12) in the RRT group versus 10.2% (<i>n</i> = 17) in the non-RRT group, respectively (HR 2.21 [1.01–4.85], <i>p</i> = 0.047)}. <b><i>Conclusions:</i></b> AKI was common among critically ill COVID-19 patients and occurred early in association with IMV. One in 6 AKI patients received RRT and 1 in 3 patients treated with RRT died in hospital. These findings provide important prognostic information for clinicians caring for these patients.

Background:Epithelial-to-mesenchymal transition (EMT) still remains an obscure event in vulvar squamous cell carcinoma (VSCC).Methods:Immunohistochemistry (IHC) expression of E-cadherin, β-catenin, Snail, Slug, Twist and Vimentin was analysed in 87 VSCC, controlled for human papillomavirus (HPV) positivity, considering tumour front and central tumour as different morphological categories from the same tumour.Results:Lower β-catenin and higher Vimentin expression was associated with invasive front when compared with the central tumour (P=0.013 and P⩽0.001, respectively). Higher expression of E-cadherin in central tumour was significantly related to absence of vascular and perineural invasion, lower invasion depth and ⩽2 lymph node involvement. Loss of β-catenin and high Slug, Snail and Twist expression was associated with HPV-negative tumours. Moreover, β-catenin lower expression associated with gain in Slug expression predicts a subgroup with worst outcome (P=0.001). Lower expression of β-catenin in both central tumour and invasive front correlated with lower overall survival (P=0.021 and P=0.011, respectively). Also, multivariate analysis showed that lower β-catenin expression was independently associated with poorer outcome (P=0.044).Conclusion:Human papillomavirus-related tumours show better prognosis and outcome; besides, they do not progress through EMT phenomenon. Immunohistochemical analysis of β-catenin in invasive tumour front is a key issue for establishing prognosis of vulva cancer.

Rare CTC clusters can be purified intact from large blood volumes with a continuous three-stage non-equilibrium inertial separation array (NISA).

The plasma membrane H(+)-ATPase from Saccharomyces cerevisiae is an enzyme that plays a very important role in the yeast physiology. The addition of protonophores, such as 2,4-dinitrophenol (DNP) and carbonyl cyanide m-chlorophenylhydrazone (CCCP), also triggers a clear in vivo activation of this enzyme. Here, we demonstrate that CCCP-induced activation of the plasma membrane H(+)-ATPase shares some similarities with the sugar-induced activation of the enzyme. Phospholipase C and protein kinase C activities are essential for this activation process while Gpa2p, a G protein involved in the glucose-induced activation of the ATPase, is not required. CCCP also induces a phospholipase C-dependent increase in intracellular calcium. Moreover, we show that the availability of extracellular calcium is required for CCCP stimulation of H(+)-ATPase, suggesting a possible connection between calcium signaling and activation of ATPase.