Publications by authors named "Sara Fossati"

14 Publications

  • Page 1 of 1

Acute kidney injury and single-dose administration of aminoglycoside in the Emergency Department: a comparison through propensity score matching.

G Ital Nefrol 2021 Jun 24;38(3). Epub 2021 Jun 24.

Department of Medicine (DAME), University of Udine, Udine, Italy; Department of Anesthesia and Intensive Care Medicine, ASUFC Hospital of Udine, Udine, Italy.

According to the Surviving Sepsis Campaign, aminoglycosides (AG) can be administered together with a β-lactam in patients with septic shock. Some authors propose administering a single dose of an AG combined with a β-lactam antibiotic in septic patients to extend the spectrum of antibiotic therapy. The aim of this study has been to investigate whether a single shot of AG when septic patients present at the Emergency Department (ED) is associated with acute kidney injury (AKI). We retrospectively enrolled patients based on a 3-year internal registry of septic patients visited in the Emergency Department (ED) of Pordenone Hospital. We compared the patients treated with a single dose of gentamicin (in addition to the β-lactam) and those who had not been treated to verify AKI incidence. 355 patients were enrolled. The median age was 71 years (IQR 60-78). Less than 1% of the patients had a chronic renal disease. The most frequent infection source was the urinary tract (31%), followed by intra-abdominal and lower respiratory tract infections (15% for both). 131 patients received gentamicin. Unmatched data showed a significant difference between the two groups in AKI (79/131, 60.3% versus 102/224, 45.5%; p=0.010) and in infectious disease specialist's consultation (77/131, 59% versus 93/224, 41.5%; p=0.002). However, after propensity score matching, no significant difference was found. Our experience shows that a single-shot administration of gentamicin upon admission to the ED does not determine an increased incidence of AKI in septic patients.
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June 2021

Artificial neural network model from a case series of COVID-19 patients: a prognostic analysis.

Acta Biomed 2021 05 12;92(2):e2021202. Epub 2021 May 12.

Department of Medicine, University of Udine, Udine, Italy; Department of Anesthesia and Intensive Care, ASUFC Santa Maria della Misericordia University Hospital of Udine, Udine, Italy.

Background And Aim: There is a need to determine which clinical variables predict the severity of COVID-19. We analyzed a series of critically ill COVID-19 patients to see if any of our dataset's clinical variables were associated with patient outcomes.

Methods: We retrospectively analyzed the data of COVID-19 patients admitted to the ICU of the Hospital in Pordenone from March 11, 2020, to April 17, 2020. Patients' characteristics of survivors and deceased groups were compared. The variables with a different distribution between the two groups were implemented in a generalized linear regression model (LM) and in an Artificial Neural Network (NN) model to verify the "robustness" of the association with mortality.

Results: In the considered period, we reviewed the data of 22 consecutive patients: 8 died. The causes of death were a severe respiratory failure (3), multi-organ failure (1), septic shock (1), pulmonary thromboembolism (2), severe hemorrhage (1). Lymphocyte and the platelet count were significantly lower in the group of deceased patients (p-value 0.043 and 0.020, respectively; cut-off values: 660/mm3; 280,000/mm3, respectively). Prothrombin time showed a statistically significant trend (p-value= 0.065; cut-off point: 16.8/sec). The LM model (AIC= 19.032), compared to the NN model (Mean Absolute Error, MAE = 0.02), was substantially alike (MSE 0.159 vs. 0.136).

Conclusions: In the context of critically ill COVID-19 patients admitted to ICU, lymphocytopenia, thrombocytopenia, and lengthening of prothrombin time were strictly correlated with higher mortality. Additional clinical data are needed to be able to validate this prognostic score.
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http://dx.doi.org/10.23750/abm.v92i2.11086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182608PMC
May 2021

Classification and analysis of outcome predictors in non-critically ill COVID-19 patients.

Intern Med J 2021 04 9;51(4):506-514. Epub 2021 Apr 9.

Department of Medicine, University of Udine, Udine, Italy.

Background: Early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients who could develop a severe form of COVID-19 must be considered of great importance to carry out adequate care and optimise the use of limited resources.

Aims: To use several machine learning classification models to analyse a series of non-critically ill COVID-19 patients admitted to a general medicine ward to verify if any clinical variables recorded could predict the clinical outcome.

Methods: We retrospectively analysed non-critically ill patients with COVID-19 admitted to the general ward of the hospital in Pordenone from 1 March 2020 to 30 April 2020. Patients' characteristics were compared based on clinical outcomes. Through several machine learning classification models, some predictors for clinical outcome were detected.

Results: In the considered period, we analysed 176 consecutive patients admitted: 119 (67.6%) were discharged, 35 (19.9%) dead and 22 (12.5%) were transferred to intensive care unit. The most accurate models were a random forest model (M2) and a conditional inference tree model (M5) (accuracy = 0.79; 95% confidence interval 0.64-0.90, for both). For M2, glomerular filtration rate and creatinine were the most accurate predictors for the outcome, followed by age and fraction-inspired oxygen. For M5, serum sodium, body temperature and arterial pressure of oxygen and inspiratory fraction of oxygen ratio were the most reliable predictors.

Conclusions: In non-critically ill COVID-19 patients admitted to a medical ward, glomerular filtration rate, creatinine and serum sodium were promising predictors for the clinical outcome. Some factors not determined by COVID-19, such as age or dementia, influence clinical outcomes.
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http://dx.doi.org/10.1111/imj.15140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250466PMC
April 2021

Prospective Study on Incidence, Risk Factors and Outcome of Recurrent Infections.

J Clin Med 2021 Mar 8;10(5). Epub 2021 Mar 8.

Infectious Diseases, ASST Lecco Hospital, 23900 Lecco, Italy.

Background: Limited and wide-ranging data are available on the recurrent infection (rCDI) incidence rate.

Methods: We performed a cohort study with the aim to assess the incidence of and risk factors for rCDI. Adult patients with a first CDI, hospitalized in 15 Italian hospitals, were prospectively included and followed-up for 30 d after the end of antimicrobial treatment for their first CDI. A case-control study was performed to identify risk factors associated with 30-day onset rCDI.

Results: Three hundred nine patients with a first CDI were included in the study; 32% of the CDI episodes (99/309) were severe/complicated; complete follow-up was available for 288 patients (19 died during the first CDI episode, and 2 were lost during follow-up). At the end of the study, the crude all-cause mortality rate was 10.7% (33 deaths/309 patients). Two hundred seventy-one patients completed the follow-up; rCDI occurred in 21% of patients (56/271) with an incidence rate of 72/10,000 patient-days. Logistic regression analysis identified exposure to cephalosporin as an independent risk factor associated with rCDI (RR: 1.7; 95% CI: 1.1-2.7, = 0.03).

Conclusion: Our study confirms the relevance of rCDI in terms of morbidity and mortality and provides a reliable estimation of its incidence.
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http://dx.doi.org/10.3390/jcm10051127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962640PMC
March 2021

mTOR as a Marker of Exercise and Fatigue in Arm.

Front Physiol 2019 11;10:1161. Epub 2019 Sep 11.

Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genoa, Italy.

Cephalopods are highly evolved marine invertebrates that colonized almost all the oceans of the world at all depths. This imposed the occurrence of several modifications of their brain and body whose muscle component represents the major constituent. Hence, studying their muscle physiology may give important hints in the context of animal biology and environmental adaptability. One major pathway involved in muscle metabolism in vertebrates is the evolutionary conserved mTOR-signaling cascade; however, its role in cephalopods has never been elucidated. mTOR is regulating cell growth and homeostasis in response to a wide range of cues such as nutrient availability, body temperature and locomotion. It forms two functionally heteromeric complexes, mTORC1 and mTORC2. mTORC1 regulates protein synthesis and degradation and, in skeletal muscles, its activation upon exercise induces muscle growth. In this work, we characterized Octopus vulgaris mTOR full sequence and functional domains; we found a high level of homology with vertebrates' mTOR and the conservation of Ser phosphorylation site required for mTORC1 activation. We then designed and tested an protocol of resistance exercise (RE) inducing fatigue in arm samples. We showed that, upon the establishment of fatigue, a transient increase in mTORC1 phosphorylation reaching a pick 30 min after exercise was induced. Our data indicate the activation of mTORC1 pathway in exercise paradigm and possibly in the regulation of energy homeostasis in octopus and suggest that mTORC1 activity can be used to monitor animal response to changes in physiological and ecological conditions and, more in general, the animal welfare.
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http://dx.doi.org/10.3389/fphys.2019.01161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749024PMC
September 2019

Use of colistin in adult patients: A cross-sectional study.

J Glob Antimicrob Resist 2020 03 15;20:43-49. Epub 2019 Jun 15.

Department of Medical and Surgical Sciences, Infectious and Tropical Diseases Unit, 'Magna Graecia' University of Catanzaro, Catanzaro, Italy.

Objectives: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB).

Methods: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed.

Results: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52-73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24-8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69-13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17-0.88; P =  0.024) was associated with use of colistin monotherapy.

Conclusion: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.
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http://dx.doi.org/10.1016/j.jgar.2019.06.009DOI Listing
March 2020

Epidemiology and Microbiology of Skin and Soft Tissue Infections: Preliminary Results of a National Registry.

J Chemother 2019 Feb 3;31(1):9-14. Epub 2018 Dec 3.

q Infectious Diseases Unit , Legnago Hospital , Verona , Italy.

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016-September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.
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http://dx.doi.org/10.1080/1120009X.2018.1536320DOI Listing
February 2019

Molecular Determinants of Cephalopod Muscles and Their Implication in Muscle Regeneration.

Front Cell Dev Biol 2017 15;5:53. Epub 2017 May 15.

Centre for Synaptic Neuroscience and Technology, Fondazione Istituto Italiano di TecnologiaGenoa, Italy.

The ability to regenerate whole-body structures has been studied for many decades and is of particular interest for stem cell research due to its therapeutic potential. Several vertebrate and invertebrate species have been used as model systems to study pathways involved in regeneration in the past. Among invertebrates, cephalopods are considered as highly evolved organisms, which exhibit elaborate behavioral characteristics when compared to other mollusks including active predation, extraordinary manipulation, and learning abilities. These are enabled by a complex nervous system and a number of adaptations of their body plan, which were acquired over evolutionary time. Some of these novel features show similarities to structures present in vertebrates and seem to have evolved through a convergent evolutionary process. (the common octopus) is a representative of modern cephalopods and is characterized by a sophisticated motor and sensory system as well as highly developed cognitive capabilities. Due to its phylogenetic position and its high regenerative power the octopus has become of increasing interest for studies on regenerative processes. In this paper we provide an overview over the current knowledge of cephalopod muscle types and structures and present a possible link between these characteristics and their high regenerative potential. This may help identify conserved molecular pathways underlying regeneration in invertebrate and vertebrate animal species as well as discover new leads for targeted tissue treatments in humans.
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http://dx.doi.org/10.3389/fcell.2017.00053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430041PMC
May 2017

The making of an octopus arm.

Evodevo 2015 7;6:19. Epub 2015 May 7.

Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.

Background: Most of our current findings on appendage formation and patterning stem from studies on chordate and ecdysozoan model organisms. However, in order to fully understand the evolution of animal appendages, it is essential to include information on appendage development from lophotrochozoan representatives. Here, we examined the basic dynamics of the Octopus vulgaris arm's formation and differentiation - as a highly evolved member of the lophotrochozoan super phylum - with a special focus on the formation of the arm's musculature.

Results: The octopus arm forms during distinct phases, including an early outgrowth from an epithelial thickening, an elongation, and a late differentiation into mature tissue types. During early arm outgrowth, uniform proliferation leads to the formation of a rounded bulge, which subsequently elongates along its proximal-distal axis by means of actin-mediated epithelial cell changes. Further differentiation of all tissue layers is initiated but end-differentiation is postponed to post-hatching stages. Interestingly, muscle differentiation shows temporal differences in the formation of distinct muscle layers. Particularly, first myocytes appear in the area of the future transverse prior to the longitudinal muscle layer, even though the latter represents the more dominant muscle type at hatching stage. Sucker rudiments appear as small epithelial outgrowths with a mesodermal and ectodermal component on the oral part of the arm. During late differentiation stages, cell proliferation becomes localized to a distal arm region termed the growth zone of the arm.

Conclusions: O. vulgaris arm formation shows both, similarities to known model species as well as species-specific patterns of arm formation. Similarities include early uniform cell proliferation and actin-mediated cell dynamics, which lead to an elongation along the proximal-distal axis. Furthermore, the switch to an adult-like progressive distal growth mode during late differentiation stages is reminiscent of the vertebrate progress zone. However, tissue differentiation shows a species-specific delay, which is correlated to a paralarval pelagic phase after hatching and concomitant emerging behavioral modifications. By understanding the general dynamics of octopus arm formation, we established a basis for further studies on appendage patterning, growth, and differentiation in a representative of the lophotrochozoan super phylum.
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http://dx.doi.org/10.1186/s13227-015-0012-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458049PMC
June 2015

Identification and Expression of Acetylcholinesterase in Octopus vulgaris Arm Development and Regeneration: a Conserved Role for ACHE?

Mol Neurobiol 2015 Aug 12;52(1):45-56. Epub 2014 Aug 12.

Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy,

Acetylcholinesterase (ACHE) is a glycoprotein with a key role in terminating synaptic transmission in cholinergic neurons of both vertebrates and invertebrates. ACHE is also involved in the regulation of cell growth and morphogenesis during embryogenesis and regeneration acting through its non-cholinergic sites. The mollusk Octopus vulgaris provides a powerful model for investigating the mechanisms underlying tissue morphogenesis due to its high regenerative power. Here, we performed a comparative investigation of arm morphogenesis during adult arm regeneration and embryonic arm development which may provide insights on the conserved ACHE pathways. In this study, we cloned and characterized O. vulgaris ACHE, finding a single highly conserved ACHE hydrophobic variant, characterized by prototypical catalytic sites and a putative consensus region for a glycosylphosphatidylinositol (GPI)-anchor attachment at the COOH-terminus. We then show that its expression level is correlated to the stage of morphogenesis in both adult and embryonic arm. In particular, ACHE is localized in typical neuronal sites when adult-like arm morphology is established and in differentiating cell locations during the early stages of arm morphogenesis. This possibility is also supported by the presence in the ACHE sequence and model structure of both cholinergic and non-cholinergic sites. This study provides insights into ACHE conserved roles during processes of arm morphogenesis. In addition, our modeling study offers a solid basis for predicting the interaction of the ACHE domains with pharmacological blockers for in vivo investigations. We therefore suggest ACHE as a target for the regulation of tissue morphogenesis.
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http://dx.doi.org/10.1007/s12035-014-8842-2DOI Listing
August 2015

Use of uteroglobin for the engineering of polyvalent, polyspecific fusion proteins.

J Biol Chem 2009 Sep 24;284(39):26646-54. Epub 2009 Jul 24.

Laboratory of Recombinant Therapeutic Proteins, Advanced Biotechnology Centre, Istituto G Gaslini, Genoa, Italy.

We report a novel strategy to engineer and express stable and soluble human recombinant polyvalent/polyspecific fusion proteins. The procedure is based on the use of a central skeleton of uteroglobin, a small and very soluble covalently linked homodimeric protein that is very resistant to proteolytic enzymes and to pH variations. Using a human recombinant antibody (scFv) specific for the angiogenesis marker domain B of fibronectin, interleukin 2, and an scFv able to neutralize tumor necrosis factor-alpha, we expressed various biologically active uteroglobin fusion proteins. The results demonstrate the possibility to generate monospecific divalent and tetravalent antibodies, immunocytokines, and dual specificity tetravalent antibodies. Furthermore, compared with similar fusion proteins in which uteroglobin was not used, the use of uteroglobin improved properties of solubility and stability. Indeed, in the reported cases it was possible to vacuum dry and reconstitute the proteins without any aggregation or loss in protein and biological activity.
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http://dx.doi.org/10.1074/jbc.M109.025924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785352PMC
September 2009

A novel human fibronectin cryptic sequence unmasked by the insertion of the angiogenesis-associated extra type III domain B.

Int J Cancer 2009 Aug;125(4):751-8

Laboratory of Cell Biology, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.

The angiogenesis-associated extra-domain B (EDB) of fibronectin (FN) is a complete type III repeat of 91 amino acids. Its expression is modulated by the alternative splicing pattern of the FN pre-mRNA. FN containing the EDB (B-FN) is undetectable in tissues of healthy adults, with rare exceptions such as the female reproductive system where tissue remodeling and angiogenesis are recurrent physiological processes. On the contrary, B-FN is expressed at high levels in neoplastic tissues and during angiogenesis; consequently, it is considered an excellent marker of angiogenesis. Here, we report on a novel FN cryptic sequence, localized on the FN type III repeat 8 (immediately downstream of the EDB) that is unmasked by the insertion of the EDB. This sequence is specifically recognized by the high-affinity monoclonal antibody, C6, that selectively recognizes B-FN by means of ELISA, immunohistochemical and Western blot assays. The variable regions of C6 were cloned and a divalent covalently linked mini-antibody was generated. Biodistribution studies using the radioiodinated C6 mini-antibody on tumor-bearing mice demonstrated an efficient tumor targeting. This antibody represents a new tool for the study of the potential biological functions of hindered sequences that the inclusion of the EDB renders accessible, and likewise makes its epitope an additional angiogenesis target.
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http://dx.doi.org/10.1002/ijc.24473DOI Listing
August 2009

Therapy-induced antitumor vaccination by targeting tumor necrosis factor alpha to tumor vessels in combination with melphalan.

Eur J Immunol 2007 Dec;37(12):3381-92

Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Varese, Italy.

Treatment of tumor-bearing mice with mouse (m)TNF-alpha, targeted to tumor vasculature by the anti-ED-B fibronectin domain antibody L19(scFv) and combined with melphalan, induces a therapeutic immune response. Upon treatment, a highly efficient priming of CD4+ T cells and consequent activation and maturation of CD8+ CTL effectors is generated, as demonstrated by in vivo depletion and adoptive cell transfer experiments. Immunohistochemical analysis of the tumor tissue demonstrated massive infiltration of CD4+ and CD8+ T cells 6 days after treatment and much earlier in the anamnestic response to tumor challenge in cured mice. In fact, the curative treatment with L19mTNF-alpha and melphalan resulted in long-lasting antitumor immune memory, accompanied by a mixed Th1/Th2-type response and significant in vitro tumor-specific cytolytic activity. Finally, the combined treatment reduced the percentage and absolute number of CD4+CD25+ regulatory T cells in the tumor-draining lymph nodes of mice responding to therapy, and this was associated with the establishment of protective immunity. These findings pave the way for alternative therapeutic strategies based on the targeted delivery of biological and pharmacological cytotoxic compounds that not only kill most of the tumor cells but, more importantly, trigger an effective and long-lasting antitumor adaptive immune response.
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http://dx.doi.org/10.1002/eji.200737450DOI Listing
December 2007

Fate of embryonal carcinoma cells injected into postimplantation mouse embryos.

Differentiation 2005 Dec;73(9-10):484-90

S.S. Animali Transgenici, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy.

Embryonal carcinoma (EC) cells, stem cells of teratocarcinoma, represent an excellent model to study the developmental mechanisms that, inappropriately reactivated, can drive tumorigenesis. EC cells are very aggressive, and grow rapidly when injected into adult syngeneic mice. However, when injected into blastocysts, they revert to normality, giving rise to chimeric animals. In order to study the ability of postimplantation embryonic environment to "normalize" tumorigenic cells, and to study their homing, we transplanted F9, Nulli-SCC1, and P19 EC cells into 8 to 15-day allogenic CD1 mouse embryos, into allogenic CD1 newborns, and into syngeneic adult mice, and evaluated tumor formation, spreading, and homing. We found that, although at all embryonic stages successful transplantation occurred, the chances of developing tumors after birth increased with the time of injection of EC cells into the embryo. In addition, using enhanced green fluorescent protein-expressing F9 cells, we demonstrated that the cells not giving rise to tumors remained latent and could be tracked down in tissues during adulthood. Our data indicate that the embryonic environment retains a certain ability to "normalize" tumor cells also during post-implantation development. This could occur through yet unknown epigenetic signals triggering EC cells' differentiation.
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http://dx.doi.org/10.1111/j.1432-0436.2005.00043.xDOI Listing
December 2005
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