Epithelial-to-mesenchymal transition (EMT) has been proposed to be important for metastatic dissemination. However, recent studies have challenged the requirement of EMT for metastasis. Here, we ...assessed in different models of primary skin squamous cell carcinomas (SCCs) whether EMT is associated with metastasis. The incidence of metastasis was much higher in SCCs presenting EMT compared to SCCs without EMT, supporting the notion that a certain degree of EMT is required to initiate the metastatic cascade in primary skin SCCs. Most circulating tumor cells presented EMT, whereas most lung metastasis did not present EMT, showing that mesenchymal-to-epithelial transition is important for metastatic colonization. In contrast, immunodeficient mice transplanted with SCCs, whether displaying EMT or not, presented metastasis. Altogether, our data demonstrate that the association of EMT and metastasis is model dependent, and metastasis of primary skin SCCs is associated with EMT.
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•Primary skin SCCs with EMT have a high incidence of metastasis•Primary skin SCCs without EMT have no metastasis•Circulating tumor cells present EMT in primary tumors with metastasis•Transplanted tumors present metastasis regardless of EMT
The role of epithelial-to-mesenchymal transition (EMT) during metastasis remains controversial. Revenco et al. show that in models of primary skin tumors, only EMT tumors are associated with metastasis. In contrast, EMT is not required to induce metastasis following the subcutaneous transplantation of tumor cells, demonstrating the context dependency of EMT for metastasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The European General Data Protection Regulation 2016/ 679 (GDPR) aims to ensure the security and privacy of individuals in the European Union (EU). Companies located within and outside of the EU must ...comply with GDPR when processing personal data of EU citizens. Medical writing includes the development of documents related to clinical research. To develop those documents, medical writers have access to personal data, including health information considered as sensitive data. Therefore, medical writing falls within the purview of GDPR and must comply with its requirements. This article is an overview of the impact of GDPR on medical writing including security measures such as anonymisation, pseudonymisation, and data minimisation techniques. It also provides an overview of the technical and organisational actions in the framework of medical writing to guarantee respect of data subjects’ rights and freedoms.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In cancer, the epithelial-to-mesenchymal transition (EMT) is associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary ...process, EMT occurs through distinct intermediate states. However, there is no direct in vivo evidence for this idea. Here we screen a large panel of cell surface markers in skin and mammary primary tumours, and identify the existence of multiple tumour subpopulations associated with different EMT stages: from epithelial to completely mesenchymal states, passing through intermediate hybrid states. Although all EMT subpopulations presented similar tumour-propagating cell capacity, they displayed differences in cellular plasticity, invasiveness and metastatic potential. Their transcriptional and epigenetic landscapes identify the underlying gene regulatory networks, transcription factors and signalling pathways that control these different EMT transition states. Finally, these tumour subpopulations are localized in different niches that differentially regulate EMT transition states.
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KISLJ, NUK, SBMB, UL, UM, UPUK
The carcinogenic effect of ionizing radiation has been evaluated based on limited populations accidently exposed to high dose radiation. In contrast, insufficient data are available on the effect of ...low dose radiation (LDR), such as radiation deriving from medical investigations and interventions, as well as occupational exposure that concern a large fraction of western populations. Using mouse skin epidermis as a model, we showed that LDR results in DNA damage in sebaceous gland (SG) and bulge epidermal stem cells (SCs). While the first commit apoptosis upon low dose irradiation, the latter survive. Bulge SC survival coincides with higher HIF‐1α expression and a metabolic switch upon LDR. Knocking down HIF‐1α sensitizes bulge SCs to LDR‐induced apoptosis, while upregulation of HIF‐1α in the epidermis, including SG SCs, rescues cell death. Most importantly, we show that LDR results in cancer formation with full penetrance in the radiation‐sensitive Patched1 heterozygous mice. Overall, our results demonstrate for the first time that LDR can be a potent carcinogen in individuals predisposed to cancer. Stem Cells 2017;35:1355–1364
The accurate maintenance of genomic integrity is essential for tissue homeostasis. Deregulation of this process leads to cancer and aging. BRCA1 is a critical mediator of this process. Here, we ...performed conditional deletion of Brca1 during epidermal development and found that BRCA1 is specifically required for hair follicle (HF) formation and for development of adult HF stem cells (SCs). Mice deficient for Brca1 in the epidermis are hairless and display a reduced number of HFs that degenerate progressively. Surprisingly, the interfollicular epidermis and the sebaceous glands remain unaffected by Brca1 deletion. Interestingly, HF matrix transient amplifying progenitors present increased DNA damage, p53 stabilization, and caspase-dependent apoptosis compared with the interfollicular and sebaceous progenitors, leading to hyperproliferation, apoptosis, and subsequent depletion of the prospective adult HF SCs. Concomitant deletion of p53 and Brca1 rescues the defect of HF morphogenesis and loss of HF SCs. During adult homeostasis, BRCA1 is dispensable for quiescent bulge SCs, but upon their activation during HF regeneration, Brca1 deletion causes apoptosis and depletion of Brca1-deficient bulge SCs. Our data reveal a major difference in the requirement of BRCA1 between different types of epidermal SCs and progenitors and during the different activation stages of adult HF SCs.
In the Republic of Moldova, more than half of all deaths due to noncommunicable diseases (NCDs) are caused by cardiovascular disease (CVD). Excess salt (sodium) and inadequate potassium intakes are ...associated with high CVD. Moreover, salt iodisation is the preferred policy to prevent iodine deficiency and associated disorders. However, there is no survey that has directly measured sodium, potassium and iodine consumption in adults in the Republic of Moldova. A national random sample of adults attended a screening including demographic, anthropometric and physical measurements. Sodium, potassium and iodine intakes were assessed by 24 h urinary sodium (UNa), potassium (UK) and iodine (UI) excretions. Knowledge, attidues and behaviours were collected by questionnaire. Eight-hundred and fifty-eight participants (326 men and 532 women, 18-69 years) were included in the analysis (response rate 66%). Mean age was 48.5 years (SD 13.8). Mean UNa was 172.7 (79.3) mmoL/day, equivalent to 10.8 g of salt/day and potassium excretion 72.7 (31.5) mmoL/day, equivalent to 3.26 g/day. Only 11.3% met the World Health Organization (WHO) recommended salt targets of 5 g/day and 39% met potassium targets (>90 mmoL/day). Whilst 81.7% declared limiting their consumption of processed food and over 70% not adding salt at the table, only 8.8% looked at sodium content of food, 31% still added salt when cooking and less than 1% took other measures to control salt consumption. Measures of awareness were significantly more common in urban compared to rural areas. Mean urinary iodine was 225 (SD: 152; median 196) mcg/24 h, with no difference between sexes. According to WHO criteria, 41.0% had adequate iodine intake. Iodine content of salt table was 21.0 (SD: 18.6) mg/kg, lower in rural than urban areas (16.7, SD = 18.6 vs. 28.1, SD = 16.5 mg/kg,
< 0.001). In most cases participants were not using iodised salt as their main source of salt, more so in rural areas. In the Republic of Moldova, salt consumption is unequivocally high, potassium consumption is lower than recommended, both in men and in women, whilst iodine intake is still inadequate in one in three people, although severe iodine deficiency is rare. Salt consumed is often not iodised.
Introduction. RVI (rotavirus infection) is the most common cause of dehydration in infants and young children. The implementation of the sentinel surveillance of RVI in infants from 2008 in the ...Republic of Moldova demonstrated the high rate of this infection (40.0%), being an argument in recommending the antirotaviral immunization in children within the National Immunization Program.
Material and methods. The study enrolled 193 children with acute diarrheal disease, included in the sentinel supervision (2012-2016) and treated in the Unit for Acute Diarrheal Diseases at Children’s Clinical Hospital no. 1. The biological material was examined by serological enzyme-linked immunosorbent assay (ELISA) and genotyping, revealed by polymerase chain reaction (PCR).
Results. The rotavirus infection was confirmed in 193 infants, of which 121 children were not vaccinated against RVI, and 72 were immunized. Depending on the genotypes encountered before and after vaccination, it was found that G9P 8, G3P8, G4P8 were detected before vaccination, although postvaccine prevailed G2P4, G4P8. In addition, the incidence of RVI is decreasing and the disease evolution is much better.
Conclusions. This article reflects the evolution of the genotypic properties of rotaviruses and the clinical-paraclinical particularities of RVI in infants, highlighting the importance of the implementation of antiretroviral immunization in children within the National Immunization Program in the Republic of Moldova.
The polarographic catalytic current in acid solutions of Mo(VI), thiosemicarbazone 2,3-dihydroxybenzaldehyde (TSC 2,3-DHBA) and chlorate ions has been investigated. The scheme of reactions, taking ...place in the solutions and on the electrode, has been proposed. The increase of the catalytic current is explained by the formation of an active intermediate complex Mo(V)×TSC 2,3-DHBA (ClO-3). The rate constant of this complex formation K = 2.56 × 106 mol-1×dm3×s-1, the activation energy Ea = 15.9 kcal×mol-1 and the reaction activation entropy ∆Sa¹ = -23.5 e.u. have been calculated.
The polarographic catalytic current in acid solutions of Mo(VI), 2,3-dihydroxybenzaldehyde (2,3-DHBA) and chlorate ions has been investigated. The scheme of reactions taking place in the solutions ...and on the electrode has been elaborated. The increase of the catalytic current is explained by the formation of the active intermediate complex Mo(V)×2,3-DHBA (ClO3-). The rate constant of formation for the active intermediate complex K = 2.5 × 106 mol-1 × dm3 × s-1, the activation energy of reaction Ea=14.0 kcal×mol-1 and the activation entropy ∆Sa¹= -28.3 e.u. have also been determined.
The polarographic behavior of the complex formed by V(V) and 2,3–dihydroxybenzaldehyde (2,3–DHBA) in the solution containing acetate buffer (pH 5,2) has been investigated. By means of a.c. ...polarography, chronovoltammetry and other techniques, it has been shown that the electrode process is complicated by the adsorption of 2,3-DHBA and its vanadium complex. The kinetic and adsorption parameters of the electrode process have been determined: adsorption equilibrium constant B= 1,32⋅105 mol-1⋅dm3, the attraction constant γ = 1,2, the maximum surface concentration Гmax = 9,10⋅10-11 mol⋅ cm-2; the share of the electrode surface occupied by one particle of the adsorbed complex S = 1,81 nm2 and the free adsorption energy ΔG = - 39,1 kJ· mol-1.
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