Publications by authors named "Joana Marinho"

11 Publications

  • Page 1 of 1

Ferric Carboxymaltose in the treatment of chemotherapy-induced anaemia: an effective, safe and cost- sparing alternative to blood transfusion.

Sci Rep 2019 12 31;9(1):20410. Epub 2019 Dec 31.

Centro Hospitalar Vila Nova de Gaia/Espinho, Medical Oncology Department, Vila Nova de Gaia, Portugal.

Anaemia is highly prevalent in cancer patients, adversely affects quality of life and impacts survival. The pathogenesis is multifactorial, with iron deficiency being a major and potentially treatable contributor. This study aimed to assess the effectiveness and economic impact of ferric carboxymaltose in chemotherapy-induced anaemia. This prospective cohort study between 2015-2016 of chemotherapy-treated patients for solid tumours, grade ≥2 anaemia and iron deficiency evaluated hematopoietic response four weeks after ferric carboxymaltose treatment. Transfusion rate of all cancer patients treated at our ambulatory unit during the two-year study period (2015-2016) was compared to a retrospective cohort (2013-2014) who received blood transfusion only. Between 2015-2016, 99 patients were included and treated with ferric carboxymaltose, the majority of whom (n = 81) had relative iron deficiency. Mean haemoglobin concentrations improved from 9.2 [6.7-10.8] g/dL to 10.6 [7.8-14.2] g/dL four weeks after treatment. A 26% reduction in the transfusion rate was observed from control retrospective to the prospective study group including ferric carboxymaltose treated patients [relative risk 0.74 (95% CI:0.66-0.83)]. The cost analysis showed a benefit for the use of ferric carboxymaltose in chemotherapy-induced anaemia. This study shows that ferric carboxymaltose is an effective, cost-saving support treatment, reducing the need for allogeneic transfusions saving blood units which are a limited resource.
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http://dx.doi.org/10.1038/s41598-019-56999-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938480PMC
December 2019

Restoration of Natural Killer Cell Antimetastatic Activity by IL12 and Checkpoint Blockade.

Cancer Res 2017 12 17;77(24):7059-7071. Epub 2017 Oct 17.

Inflammation research, Institute of Experimental Immunology, University of Zurich, Switzerland.

Immune checkpoint therapies target tumor antigen-specific T cells, but less is known about their effects on natural killer (NK) cells, which help control metastasis. In studying the development of lung metastases, we found that NK cells lose their cytotoxic capacity and acquire a molecular signature defined by the expression of coinhibitory receptors. In an effort to overcome this suppressive mechanism, we evaluated NK cell responses to the immunostimulatory cytokine IL12. Exposure to IL12 rescued the cytotoxicity of NK cells but also led to the emergence of an immature NK cell population that expressed high levels of the coinhibitory molecules PD-1, Lag-3, and TIGIT, thereby limiting NK cell-mediated control of pulmonary metastases. Notably, checkpoint blockade therapy synergized with IL12 to fully enable tumor control by NK cells, demonstrating that checkpoint blockers are not only applicable to enhance T cell-mediated immunotherapy, but also to restore the tumor-suppressive capacity of NK cells. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-1032DOI Listing
December 2017

TGFβ/Activin signalling is required for ribosome biogenesis and cell growth in Drosophila salivary glands.

Open Biol 2017 01;7(1)

I3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4150-180, Portugal

Signalling by TGFβ superfamily factors plays an important role in tissue growth and cell proliferation. In Drosophila, the activity of the TGFβ/Activin signalling branch has been linked to the regulation of cell growth and proliferation, but the cellular and molecular basis for these functions are not fully understood. In this study, we show that both the RII receptor Punt (Put) and the R-Smad Smad2 are strongly required for cell and tissue growth. Knocking down the expression of Put or Smad2 in salivary glands causes alterations in nucleolar structure and functions. Cells with decreased TGFβ/Activin signalling accumulate intermediate pre-rRNA transcripts containing internal transcribed spacer 1 regions accompanied by the nucleolar retention of ribosomal proteins. Thus, our results show that TGFβ/Activin signalling is required for ribosomal biogenesis, a key aspect of cellular growth control. Importantly, overexpression of Put enhanced cell growth induced by Drosophila Myc, a well-characterized inducer of nucleolar hypertrophy and ribosome biogenesis.
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http://dx.doi.org/10.1098/rsob.160258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303274PMC
January 2017

Insulin resistance, dyslipidemia and cardiovascular changes in a group of obese children.

Arq Bras Cardiol 2015 Apr 23;104(4):266-73. Epub 2015 Jan 23.

Instituto Biomédico de Investigação da Luz e Imagem, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.

Introduction: Obesity-related comorbidities are present in young obese children, providing a platform for early adult cardiovascular disorders.

Objectives: To compare and correlate markers of adiposity to metabolic disturbances, vascular and cardiac morphology in a European pediatric obese cohort.

Methods: We carried out an observational and transversal analysis in a cohort consisting of 121 obese children of both sexes, between the ages of 6 and 17 years. The control group consisted of 40 children with normal body mass index within the same age range. Markers of adiposity, plasma lipids and lipoproteins, homeostasis model assessment-insulin resistance, common carotid artery intima-media thickness and left ventricular diameters were analyzed.

Results: There were statistically significant differences between the control and obese groups for the variables analyzed, all higher in the obese group, except for age, high-density lipoprotein cholesterol and adiponectin, higher in the control group. In the obese group, body mass index was directly correlated to left ventricular mass (r=0.542; p=0.001), the homeostasis model assessment-insulin resistance (r=0.378; p=<0.001) and mean common carotid artery intima-media thickness (r=0.378; p=<0.001). In that same group, insulin resistance was present in 38.1%, 12.5% had a combined dyslipidemic pattern, and eccentric hypertrophy was the most common left ventricular geometric pattern.

Conclusions: These results suggest that these markers may be used in clinical practice to stratify cardiovascular risk, as well as to assess the impact of weight control programs.
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http://dx.doi.org/10.5935/abc.20140206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415862PMC
April 2015

Pro-inflammatory triggers in childhood obesity: correlation between leptin, adiponectin and high-sensitivity C-reactive protein in a group of obese Portuguese children.

Rev Port Cardiol 2014 Nov 11;33(11):691-7. Epub 2014 Nov 11.

Laboratório de Fisiologia, Instituto de Imagem Biomédica e Ciências da Vida, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.

Introduction: Pediatric obesity is increasingly prevalent in the Portuguese population. Adipocyte dysfunction results in the expression of pro-inflammatory mediators that are responsible for the low-grade inflammatory process that characterizes obesity.

Objectives: The aim of this study was to investigate the relationship between markers of adiposity, inflammation and adipokines in a Portuguese obese pediatric population.

Methods: One hundred and twenty children of both sexes, aged 6-17 years, were included in this study. The control group consisted of 41 healthy normal-weight children. The variables analyzed were age, gender, body mass index, waist circumference, fat mass percentage, high-sensitivity C-reactive protein (hs-CRP), leptin and adiponectin.

Results: There were significant differences between controls and obese children for all parameters analyzed. In the obese group, after controlling for age and gender, hs-CRP (p=0.041), adiponectin (p=0.019) and leptin (p<0.001) still showed significant statistical differences. A direct correlation was found between hs-CRP, leptin, body mass index and waist circumference, the strongest being with leptin (r=0.568; p<0.001). This trend remained statistically significant, regardless of gender or pubertal age.

Conclusions: Considering the role of leptin, adiponectin and hs-CRP in the genesis of endothelial dysfunction, they may be used in clinical practice for risk stratification, as well as in the assessment of weight control programs.
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http://dx.doi.org/10.1016/j.repc.2014.04.004DOI Listing
November 2014

Giant major aortopulmonary collateral artery: a rare cause of heart murmur in newborns.

Rev Port Cardiol 2014 Jul-Aug;33(7-8):483-5. Epub 2014 Jul 31.

Serviço de Cardiologia, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

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http://dx.doi.org/10.1016/j.repc.2014.02.002DOI Listing
July 2016

Accidental finding of a giant right coronary artery aneurysm associated with a fistula to the right atrium.

Cardiol Young 2014 Jun 22;24(3):528-30. Epub 2013 May 22.

Pediatric Cardiology Department, Pediatric Hospital Carmona da Mota, CHUC EPE, Coimbra, Portugal.

Coronary artery fistulae are uncommon but may be haemodynamically significant, being an incidental finding in 0.1-0.2% of coronary angiograms. Even rarer is the association between fistulae and non-atherosclerotic coronary artery aneurysms. They most frequently originate in the right coronary artery, and the right cardiac chambers are the most common draining chambers. Most children are asymptomatic, whereas those older than 20 years may present with signs of congestive heart failure, infective endocarditis, myocardial ischaemia, or aneurysm rupture. Management is either surgical or via percutaneous means. We report the case of a 5-year-old child referred for assessment of an asymptomatic cardiac murmur. The echocardiographic evaluation showed an enlarged right atrium, a fenestrated atrial septal defect, and a giant right coronary artery aneurysm with a fistulous tract that appeared to drain directly into the right atrium. Computed angiocardiac tomography and cardiac catherisation confirmed the presence of a large right coronary fistula originating from the right coronary aneurysm draining into the right atrium. The patient underwent surgical ligation of the fistula and the post-operative course has been uneventful. He is currently on double antiaggregation therapy.
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http://dx.doi.org/10.1017/S1047951113000589DOI Listing
June 2014

The nucleolar protein Viriato/Nol12 is required for the growth and differentiation progression activities of the Dpp pathway during Drosophila eye development.

Dev Biol 2013 May 14;377(1):154-65. Epub 2013 Feb 14.

Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto 4150-180, Portugal.

Drosophila Decapentaplegic (Dpp), a member of the BMP2/4 class of the TGF-βs, is required for organ growth, patterning and differentiation. However, much remains to be understood about the mechanisms acting downstream of these multiple roles. Here we investigate this issue during the development of the Drosophila eye. We have previously identified viriato (vito) as a dMyc-target gene encoding a nucleolar protein that is required for proper tissue growth in the developing eye. By carrying out a targeted in vivo double-RNAi screen to identify genes and pathways functioning with Vito during eye development, we found a strong genetic interaction between vito and members of the Dpp signaling pathway including the TGF-β receptors tkv (type I), put (type II), and the co-Smad medea (med). Analyzing the expression of the Dpp receptor Tkv and the activation pattern of the pathway's transducer, p-Mad, we found that vito is required for a correct signal transduction in Dpp-receiving cells. Overall, we validate the use of double RNAi to find specific genetic interactions and, in particular, we uncover a link between the Dpp pathway and Vito, a nucleolar component. vito would act genetically downstream of Dpp, playing an important role in maintaining a sufficient level of Dpp activity for the promotion of eye disc growth and regulation of photoreceptor differentiation in eye development.
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http://dx.doi.org/10.1016/j.ydbio.2013.02.003DOI Listing
May 2013

The Drosophila Nol12 homologue viriato is a dMyc target that regulates nucleolar architecture and is required for dMyc-stimulated cell growth.

Development 2011 Jan;138(2):349-57

Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto 4150-180, Portugal.

The nucleolus is a subnuclear factory, the activity of which is required beyond ribosome biogenesis for the regulation of cell growth, death and proliferation. In both Drosophila and mammalian cells, the activity of the nucleolus is regulated by the proto-oncogene Myc. Myc induces the transcription of genes required for ribosome biogenesis and the synthesis of rRNA by RNA polymerase I, a nucleolar event that is rate limiting for cell growth. Here, we show that the fruit fly Nol12 homologue Viriato is a key determinant of nucleolar architecture that is required for tissue growth and cell survival during Drosophila development. We further show that viriato expression is controlled by Drosophila Myc (dMyc), and that the ability of dMyc to stimulate nucleolar and cellular growth depends on viriato expression. Therefore, viriato acts downstream of dMyc to ensure a coordinated nucleolar response to dMyc-induced growth and, thereby, normal organ development.
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http://dx.doi.org/10.1242/dev.054411DOI Listing
January 2011

4'-methoxy-2-styrylchromone a novel microtubule-stabilizing antimitotic agent.

Biochem Pharmacol 2008 Feb 22;75(4):826-35. Epub 2007 Oct 22.

CEQOFFUP-Centro de Estudos de Química Orgânica, Fitoquímica e Farmacologia da Universidade do Porto, Porto, Portugal.

4'-methoxy-2-styrylchromone, a new synthetic chromone was identified as a selective proliferation inhibitor of human tumor (MCF-7 and NCI-H460) cell lines than to non-tumor cells (MRC-5). The antiproliferative activity of this chromone was also extensive to peripheral human lymphocytes. 4'-Methoxy-2-styrylchromone was found to block tumor cells in the G2/M phase of the cell cycle. The G2/M arrest of NCI-H460 cells was dose- and time-dependent, reaching a maximum after 12-h treatment while MCF-7 cells reached the maximum value of G2/M accumulation only after a 24-h treatment. Chromone-treated cells evidenced a high frequency of cells in prometaphase, indicating progression beyond G2 and arrest early in mitosis. This mitotic arrest was associated with abnormal mitotic spindles characterized by the formation of a monopolar structure, suggesting that the chromone interferes with microtubules. The results of an in vitro tubulin polymerization assay showed that this chromone stabilizes microtubules in a manner similar to paclitaxel.
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http://dx.doi.org/10.1016/j.bcp.2007.10.014DOI Listing
February 2008