Papers by Christian Ramos
Revista medica de Chile, 2011
BACKGROUND GIMEMA ALL 0288 trial was designed to evaluate the impact of a 7-day prednisone (PDN) ... more BACKGROUND GIMEMA ALL 0288 trial was designed to evaluate the impact of a 7-day prednisone (PDN) pretreatment on complete remission of acute lymphoblastic leukemia. We adopted this trial in 2007. AIM To evaluate the results of treatment in two cohorts of patients with acute lymphoblastic leukemia, treated from 2007 to January 2009 and from February to December 2009. MATERIAL AND METHODS We studied 99 patients treated in the first period (58 males) and 54 patients treated in the second period (33 males) The age of patients ranged from 16 to 60 years and 70% of patients were of high risk. BCR/ABL fusion transcript was present in 12% of patients. RESULTS Remission rates were 61 and 51% for patients of the first and second group of treatment, respectively. The main cause of death were infections during the induction period. There were 49 relapses, mainly detected in the blood marrow. Global and event free 34 months survival were 32 and 30% respectively. Multivariate analysis disclosed r...
This work shows the results of investigations performed with the objective of optimizing methane ... more This work shows the results of investigations performed with the objective of optimizing methane production from dairy wastewater in anaerobic reactors through the adaptation of microbial populations towards a more complete degradation of high methane yielding substrates. The innovative aspect of this work lies on the use of a novel operating mode – intermittent operation – that allows a raising of methane yield of over 20% in relation to what is obtained with conventional (continuous) systems with the same wastewater purification efficiencies. Results from molecular techniques confirm that this improvement in methane production is due to the development in the intermittent system of a microbial population highly adapted to the metabolization of lipids which are the substrates with higher methane yield potential in dairy wastewater.
Educação 2.0: desafios e conquistas, 2021
Journal of Global Oncology, 2019
PURPOSE Limited information is available on multiple myeloma (MM), chronic lymphocytic leukemia (... more PURPOSE Limited information is available on multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL) management in Latin America. The primary objective of the Hemato-Oncology Latin America (HOLA) study was to describe patient characteristics and treatment patterns of Latin American patients with MM, CLL, and NHL. METHODS This study was a multicenter, retrospective, medical chart review of patients with MM, CLL, and NHL in Latin America identified between January 1, 2006, and December 31, 2015. Included were adults with at least 1 year of follow-up (except in cases of death within 1 year of diagnosis) treated at 30 oncology hospitals (Argentina, 5; Brazil, 9; Chile, 1; Colombia, 5; Mexico, 6; Panama/Guatemala, 4). RESULTS Of 5,140 patients, 2,967 (57.7%) had NHL, 1,518 (29.5%) MM, and 655 (12.7%) CLL. Median follow-up was 2.2 years for MM, 3.0 years for CLL, and 2.2 years for NHL, and approximately 26% died during the study observation period. Most pa...
Background: Holobionts are defined as a host and its microbiota, and there is not a consensus abo... more Background: Holobionts are defined as a host and its microbiota, and there is not a consensus about their status as a unit of selection. The “it’s the song, not the singer” theory proposes that functional traits, instead of taxonomical composition, could be preserved across generations if interspecies interaction patterns perpetuate themselves. We used a novel combination of community level analysis on the functional composition of microbiota-communities to test this theory by using empirical and simulated data. We tested the conservation of functional composition across generations using mosquito and plant datasets. Then, we tested if there is a change of functional composition over time within a generation in human datasets. Finally, we simulated microbiota communities with different amounts of pairwise interspecies interactions and initial configurations to investigate if the interactions can lead to multiple stable community compositions. Results: Our results suggest that the ve...
Global & Regional Health Technology Assessment: Italian; Northern Europe and Spanish, 2017
Original rESEarCH artiClE alteraciones cualitativas en las 3 series hematopoyéticas y riesgo de t... more Original rESEarCH artiClE alteraciones cualitativas en las 3 series hematopoyéticas y riesgo de transformación a leucemia mieloide aguda. En el pasado el SMD fue llamado pre-leucemia o leucemia quiescente. Los SMDs estuvieron anteriormente clasificados como una enfermedad de bajo potencial maligno, ahora que se conoce más de la enfermedad, se le considera una forma de cáncer (1, 2). Se estima que la incidencia de SMD es de 4-12 casos por 100 mil individuos/año; la incidencia se incrementa significativamente con la edad avanzada donde puede llegar hasta los 30 a 60 casos × 100 mil individuos mayores de 70 años de edad. La aparición en la edad pediátrica y en el adulto joven es poco frecuente (1, 3). Existen 2 tipos de SMD, el primario que es de etiología generalmente desconocida y el secundario que corresponde al 20% de los MDS, este último tipo se asocia al tratamiento previo con esquemas de quimioterapia que contienen agentes alquilantes, epipodofilotoxinas y antraciclinas. Otros
OncoTargets and Therapy, 2019
Objective: Approximately 40-50% of patients with acute myeloid leukaemia (AML) have been reported... more Objective: Approximately 40-50% of patients with acute myeloid leukaemia (AML) have been reported to present with a normal karyotype and a variable disease-free period, most likely due to the molecular heterogeneity presented by these patients. A variety of mutations have been identified at the molecular level, such as those in the IDH1/2 gene, which causes a gain of function of the isocitrate dehydrogenase enzyme, generating high levels of the (R)-2hydroxyglutarate oncometabolite, which competitively inhibits dioxygenase enzymes. Therefore, the objective of this study was to evaluate the incidence of IDH1/2 gene mutations in AML patients and their impact on survival. Materials and methods: A total of 101 patients with a diagnosis of AML were included; mononuclear cells were obtained for DNA extraction and purification. Mutations were detected using TaqMan™ competitive allele-specific probes (castPCR™). Overall survival curves were plotted using IBM SPSS Statistics 23 software. Results: The frequency of IDH gene mutations was 19.8%. For the IDH1 gene, 13.8% of the mutations identified included R132H, V178I, G105G and R132C. The frequency of mutations of the IDH2 gene was 5.9%; the variants included R172K and R140Q. The mean survival time in patients without IDH1 gene mutations was 173.15 days (120.20-226.10), while the mean survival time for patients with mutations was 54.95 days (9.7-100.18), p = 0.001. Conclusion: The frequency of IDH1 and IDH2 gene mutations in the sample was similar to that reported in other studies. The analysis of these mutations in AML patients is of great importance as a prognostic factor due to their impact on survival and their use as potential therapeutic targets or as targets of inhibitors of IDH1(Ivosidenib, Tibsovo) and IDH2 (Enasidenib, Idhifa).
Building and Environment, 2018
Indoor environmental conditions, including acoustic, lighting, and thermal conditions, can impact... more Indoor environmental conditions, including acoustic, lighting, and thermal conditions, can impact the experience of occupants. How should these conditions be combined to optimize indoor environments for occupants? Living labs, in which study participants occupy a simulated real-world environment for an extended period, offer a new way to test the interactive effects of environmental conditions. In a proof-of-concept study, we tested whether varying combinations of environmental conditions in a simulated open-office environment would affect the experience of its occupants. Six different environmental "scenes"-combinations of acoustic, lighting, and thermal conditions-were varied weekly over 18 weeks. One scene had environmental conditions commonly found in offices, including participants' previous office, and served as the baseline against which the other scenes were compared. We tested the effects of office environmental conditions on occupants' satisfaction and workday experience in the environment. Further, we tested whether the influence of the environment would extend outside of the time spent at work to affect occupants' feelings and health behaviors. Changes in office environmental conditions affected occupants' environmental satisfaction and their workday experience. Outside of the office, environmental conditions affected people's feelings (e.g., happiness) and health behaviors (reported sleep problems). These findings demonstrate that living labs offer a powerful methodology to test the interactive effects of environmental conditions on occupants' experience, both inside and outside the lab.
Revista médica de Chile, 2017
Usefulness of imaging studies in prostate cancer. Analysis of 241 patients Background: The role o... more Usefulness of imaging studies in prostate cancer. Analysis of 241 patients Background: The role of staging studies in patients with prostate cancer (PCa) is a topic of discussion. Aim: To evaluate the usefulness of imaging studies in patients with prostate cancer. Material and Methods: We reviewed the pathology service records to identify patients with prostate cancer diagnosed between 2003 and 2013. We reviewed the electronic medical records of those patients identified as having a prostate cancer. Patients were grouped according D'amico's classification of cancer dissemination risk. We analized the frequency of imaging studies requested and their efficacy to detect metastases in each risk group. Results: We identified 241 patients with a mean age of 67 years. Fifty two percent of patients were classified as low-risk, 32% as intermediate-risk and 16% as high risk. At least one imaging study was requested to 64% of patients (49, 78 and 87% of patients with low, intermediate and high risk respectively). Among the 155 patients in whom an imaging study was requested, no metastases were found in the low risk group. On the other hand, dissemination was found in 7% of the intermediate-risk group and 62% of the high-risk group. Conclusions: Half of patients with prostate cancer were classified as low risk. In half of this group of low risk patients, staging studies were requested and the probability of detecting metastases was low or nil. The odds of detecting metastases increased in higher risk groups.
Cancer Research, 2015
Cancer stem cells (CSCs) are related with cancer initiation, metastasis, resistance and recurrenc... more Cancer stem cells (CSCs) are related with cancer initiation, metastasis, resistance and recurrence, by regulating their environment in different ways, including the release of exosomes that modify surrounding and distant cells. Exosomes contain, among other molecules, miRNAs. By identifying the entire spectrum of miRNAs included in exosomes from prostate cancer (PCa) cells by next generation sequencing (NGS), is possible to identify miRNAs specifically released by CSCs, and those related with microenvironment regulation. We stablished adherent primary cell cultures (bulk cells) from PCa tissue from 5 patients. Later, from these cells we obtained CSCs enriched prostatospheres. From bulk and CSCs cultures we purified exosomes by precipitation (ExoQuick-TC, SBI) for miRNAs extraction (mirVana, Ambion). Quality of miRNAs was assessed by Bioanalizer (Agilent Technologies). NGS was performed in the Illumina platform (MiSeq, Illumina) according to manufacturer instructions. Bioinformatic a...
PLoS ONE, 2012
Small non-coding regulatory RNAs (sRNAs) post-transcriptionally affect multiple phenotypes in pro... more Small non-coding regulatory RNAs (sRNAs) post-transcriptionally affect multiple phenotypes in prokaryotes and eukaryotes, yet most of the underlying regulatory mechanisms and the nature of the target mRNAs remain unclear. Here we report the identification and functional analysis of the novel cis-encoded sRNA h2cR, from the human opportunistic pathogen Burkholderia cenocepacia J2315. The sRNA was found to negatively regulate the hfq2 mRNA, through binding to part of the 59-UTR region of the hfq2 mRNA, resulting in accelerated hfq2 mRNA decay and reduced protein levels in exponentially growing cells. Both the h2cR transcript and the hfq2 mRNA are stabilized by the other B. cenocepacia RNA chaperone, Hfq. Infection experiments using the nematode Caenorhabditis elegans revealed that down-regulation of Hfq2 by h2cR decreases the B. cenocepacia ability to colonize and persist within the nematode, suggesting a role for h2cR on bacterial persistence in the host.
PLoS ONE, 2014
Small non-coding RNAs (sRNAs) are important players of gene expression regulation in bacterial pa... more Small non-coding RNAs (sRNAs) are important players of gene expression regulation in bacterial pathogens. MtvR is a 136nucleotide long sRNA previously identified in the human pathogen Burkholderia cenocepacia J2315 and with homologues restricted to bacteria of the Burkholderia cepacia complex. In this work we have investigated the effects of expressing MtvR in Escherichia coli and Pseudomonas aeruginosa. Results are presented showing that MtvR negatively regulates the hfq mRNA levels in both bacterial species. In the case of E. coli, this negative regulation is shown to involve binding of MtvR to the 59-UTR region of the hfq Ec mRNA. Results presented also show that expression of MtvR in E. coli and P. aeruginosa originates multiple phenotypes, including reduced resistance to selected stresses, biofilm formation ability, and increased susceptibility to various antibiotics.
1st Portuguese Biomedical Engineering Meeting, 2011
Page 1. A RNomics-based strategy identifies regulatory small RNAs in Burkholderia cepacia complex... more Page 1. A RNomics-based strategy identifies regulatory small RNAs in Burkholderia cepacia complex Christian G. Ramos, Sílvia A. Sousa, André M. Grilo, Paulo JP Da Costa, Joana R. Feliciano and Jorge H. Leitão* IBB Institute ...
Neuro-Oncology, 2011
We explored the associations of aberrant DNA methylation patterns in 12 candidate genes with adul... more We explored the associations of aberrant DNA methylation patterns in 12 candidate genes with adult glioma subtype, patient survival, and gene expression of enhancer of zeste human homolog 2 (EZH2) and insulin-like growth factor-binding protein 2 (IGFBP2). We analyzed 154 primary glioma tumors (37 astrocytoma II and III, 52 primary glioblastoma multiforme (GBM), 11 secondary GBM, 54 oligodendroglioma/oligoastrocytoma II and III) and 13 nonmalignant brain tissues for aberrant methylation with quantitative methylation-specific PCR (qMS-PCR) and for EZH2 and IGFBP2 expression with quantitative reverse transcription PCR (qRT-PCR). Global methylation was assessed by measuring long interspersed nuclear element-1 (LINE1) methylation. Unsupervised clustering analyses yielded 3 methylation patterns (classes). Class 1 (MGMT, PTEN, RASSF1A, TMS1, ZNF342, EMP3, SOCS1, RFX1) was highly methylated in 82% (75/91) of lower-grade astrocytic and oligodendroglial tumors, 73% (8/11) of secondary GBMs, and 12% (6/52) of primary GBMs. The primary GBMs in this class were early onset (median age 37 years). Class 2 (HOXA9 and SLIT2) was highly methylated in 37% (19/52) of primary GBMs. None of the 10 genes for class 3 that were differentially methylated in classes 1 and 2 were hypermethylated in 92% (12/13) of nonmalignant brain tissues and 52% (27/52) of primary GBMs. Class 1 tumors had elevated EZH2 expression but not elevated IGFBP2; class 2 tumors had both high IGFBP2 and high EZH2 expressions. The gene-specific hypermethylation class correlated with higher levels of global LINE1 methylation and longer patient survival times. These findings indicate a generalized hypermethylation phenotype in glioma linked to improved survival and low IGFBP2. DNA methylation markers are useful in characterizing distinct glioma subtypes and may hold promise for clinical applications.
Microbiology, 2009
TheBurkholderia cepaciacomplex (Bcc) emerged as problematic opportunistic pathogens to cystic fib... more TheBurkholderia cepaciacomplex (Bcc) emerged as problematic opportunistic pathogens to cystic fibrosis (CF) patients. Although several virulence factors have been identified in Bcc, the knowledge of their relative contribution to Bcc pathogenicity remains scarce. In this work, we describe the identification and characterization of aB. cepaciaIST408 mutant containing a disruption in thehfqgene. In other bacteria, Hfq is a global regulator of metabolism, acting as an RNA chaperone involved in the riboregulation of target mRNAs by small regulatory non-coding RNAs (sRNAs). TheB. cepaciaHfq protein was overproduced as a histidine-tagged derivative, and we show evidence that the protein forms hexamers and binds sRNAs. When providedin trans, theB. cepaciaIST408hfqgene complemented theEscherichia coli hfqmutant strain GS081. Our results also show that theB. cepacia hfqmutant is more susceptible to stress conditions mimicking those faced by Bcc bacteria when infecting the CF host. In additio...
Microbial Pathogenesis, 2010
Burkholderia cenocepacia is one of the most virulent species of the Burkholderia cepacia complex,... more Burkholderia cenocepacia is one of the most virulent species of the Burkholderia cepacia complex, a group of bacteria that emerged as important pathogens, especially to cystic fibrosis (CF) patients. In this study, we report the identification and characterization of a mutant strain derived form the CF isolate Burkholderia cenocepacia K56-2, carrying a plasposon insertion in a gene, located in a 3516 bp chromosomal region with an atypical G þ C content, encoding a 80 amino acid putative regulatory protein named Pbr. Besides its inability to produce phenazines, the B. cenocepacia K56-2 pbr mutant exhibited a pleiotropic phenotype, including impaired survival to oxidative and osmotic stress, aromatic amino acid and prolonged nutrient starvation periods. In addition, the pbr mutant exhibited decreased virulence the nematode Caenorhabditis elegans. Altogether, our results demonstrate the involvement of Pbr on the regulation of phenazine biosynthesis, and an important role for this regulatory protein on several cellular processes related to stress resistance and virulence.
The Journal of Urology, 1999
The Journal of Urology, 1999
The Journal of Urology, 1999
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Papers by Christian Ramos