https://cancerbiologyprogram.med.wayne.edu/pdfs/hallmarks_cancer_article.pdf

Hallmarks of cancer: the next generation.

A large body of literature is available on wound healing in humans. Nonetheless, a standardized ex vivo wound model without disruption of the dermal compartment has not been put forward with compelling justification. Here, we present a novel wound model based on application of negative pressure and its effects for epidermal regeneration and immune cell behaviour. Importantly, the basement membrane remained intact after blister roof removal and keratinocytes were absent in the wounded area. Upon six days of culture, the wound was covered with one to three-cell thick K14+Ki67+ keratinocyte layers, indicating that proliferation and migration were involved in wound closure. After eight to twelve days, a multi-layered epidermis was formed expressing epidermal differentiation markers (K10, filaggrin, DSG-1, CDSN). Investigations about immune cell-specific manners revealed more T cells in the blister roof epidermis compared to normal epidermis. We identified several cell populations in blister roof epidermis and suction blister fluid that are absent in normal epidermis which correlated with their decrease in the dermis, indicating a dermal efflux upon negative pressure. Together, our model recapitulates the main features of epithelial wound regeneration, and can be applied for testing wound healing therapies and investigating underlying mechanisms.

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Re-epithelialization and immune cell behaviour in an ex vivo human skin model.

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

SOLID tumors are composed of two discrete but interdependent compartments: the malignant cells themselves and the stroma that they induce and in which they are dispersed.1 , 2 In tumors of epitheli...

Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing.

Hantaviruses are enveloped RNA viruses each carried by a specific rodent species. Three hantaviruses, Puumala, Dobrava, and Saaremaa viruses, are known to cause haemorrhagic fever with renal syndrome. In Europe. Puumala causes a generally mild disease, nephropathia epidemica, which presents most commonly with fever, headache, gastrointestinal symptoms, impaired renal function, and blurred vision, whereas Dobrava infections often also have haemorrhagic complications. There are few available data about the clinical picture of confirmed Saaremaa infections, but epidemiological evidence suggests that it is less pathogenic than Dobrava, and that Saaremaa infections are more similar to nephropathia epidemica caused by Puumala. Along with its rodent host, the bank vole (Clethrionomys glareolus), Puumala is reported throughout most of Europe (excluding the Mediterranean region), whereas Dobrava, carried by the yellow-necked mouse (Apodemus flavicollis), and Saaremaa, carried by the striped field mouse (Apodemus agrarius), are reported mainly in eastern and central Europe. The diagnosis of acute hantavirus infection is based on the detection of virus-specific IgM. Whereas Puumala is distinct, Dobrava and Saaremaa are genetically and antigenically very closely related and were previously thought to be variants of the same virus. Typing of a specific hantavirus infection requires neutralisation antibody assays or reverse transcriptase PCR and sequencing.

Hantavirus infections in Europe.

Sequential appearance of fibronectin and collagen in experimental granulation tissue.

Activation of fibroblasts in cancer stroma.

Introduction. The isolation by Ho Wang Lee and collaborators of the virus causing Korean haemorrhagic fever, now called Hantaan virus (HTN), from the lungs of striped field mice (Apodemus agrarius) in 1976 (Lee & Lee, 1976) launched a new era in the study of haemorrhagic fever with renal syndrome (HFRS) throughout the world. This was soon followed by the discovery of the causative agent of the European form of HFRS, nephropathia epidemica, now known as Puumala virus (PUU) (Brummer-Korvenkontio et al., 1980), and of the urban rat virus, Seoul virus (SEO) (Lee et al., 1980). The identification in 1993 of Sin Nombre virus (SN) as the causative agent of hantavirus-associated pulmonary syndrome (HPS) (Nichol et al., 1993a) led to intensive search for further hantaviruses and as a result today a total of as many as 16 well-established sero/genotypes may be listed.

Hantaviruses: genome structure, expression and evolution.

Ezrin, previously also known as cytovillin, p81, and 80K, is a cytoplasmic protein enriched in microvilli and other cell surface structures. Ezrin is postulated to have a membrane-cytoskeleton linker role. Recent findings have also revealed that the NH2-terminal domain of ezrin is associated with the plasma membrane and the COOH-terminal domain with the cytoskeleton (Algrain, M., O. Turunen, A. Vaheri, D. Louvard, and M. Arpin. 1993. J. Cell Biol. 120: 129-139). Using bacterially expressed fragments of ezrin we now demonstrate that ezrin has an actin-binding capability. We used glutathione-S-transferase fusion proteins of truncated ezrin in affinity chromatography to bind actin from the cell extract or purified rabbit muscle actin. We detected a binding site for filamentous actin that was localized to the COOH-terminal 34 amino acids of ezrin. No binding of monomeric actin was detected in the assay. The region corresponding to the COOH-terminal actin-binding site in ezrin is highly conserved in moesin, actin-capping protein radixin and EM10 protein of E. multilocularis, but not in merlin/schwannomin. Consequently, this site is a potential actin-binding site also in the other members of the protein family. Furthermore, the actin-binding site in ezrin shows sequence homology to the actin-binding site in the COOH terminus of the beta subunit of the actin-capping protein CapZ and one of the potential actin-binding sites in myosin heavy chain. The actin-binding capability of ezrin supports its proposed role as a membrane-cytoskeleton linker.

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Antti Vaheri

Papers

Hantavirus infections in Europe.

Sequential appearance of fibronectin and collagen in experimental granulation tissue.

Activation of fibroblasts in cancer stroma.

Hantaviruses: genome structure, expression and evolution.

Ezrin has a COOH-terminal actin-binding site that is conserved in the ezrin protein family.