Publications by authors named "Rommel Mário Rodriguez Burbano"

43 Publications

Oral and oropharyngeal diffuse large B-cell lymphoma and high-grade B-cell lymphoma: A clinicopathologic and prognostic study of 69 cases.

Oral Surg Oral Med Oral Pathol Oral Radiol 2020 Nov 20. Epub 2020 Nov 20.

Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba/Brazil; Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Department of Oral Biology and Oral Pathology, University of Pretoria, Pretoria, South Africa. Electronic address:

Objective: The objective of this study was to describe the clinicopathological, molecular, and prognostic features of oral/oropharyngeal diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma.

Study Design: All cases were retrieved from 7 Brazilian institutions. Immunohistochemical reactions were performed to confirm the diagnoses and to categorize the tumors. In situ hybridization was used to detect Epstein-Barr virus (EBV) and fluorescence in situ hybridization was used to identify gene rearrangements.

Results: Most cases involved the oral cavity (76.8%). Males and females, with a mean age of 60 years, were evenly affected. Tumors mostly presented as painful swellings. Forty cases represented germinal center B-cell type (58%). Five cases presented double-hit translocation and 3 harbored rearrangement for MYC/BCL2/BCL6. EBV was detected in 3 cases (4.3%). The 5-year overall survival was 44.4%. Female sex, presence of pain and ulcer, microscopic "starry sky pattern" and necrosis, co-expression of c-Myc/Bcl2, and translocation of MYC were associated with a lower survival in univariate analysis (P = .05, P = .01, P = .01, P = .03, P = .05, P = .006, P = .05, respectively).

Conclusion: Patients affected by oral/oropharyngeal DLBCL have a low survival rate. High-grade B-cell lymphoma (17.7%) and EBV-positive DLBCL, not otherwise specified (4.3%) account for a small number of cases.
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http://dx.doi.org/10.1016/j.oooo.2020.11.005DOI Listing
November 2020

Detection of deletions in 1q25, 1p36 and 1pTEL and chromosome 17 aneuploidy in oral epithelial dysplasia and oral squamous cell carcinoma by fluorescence in situ hybridization (FISH).

Oral Oncol 2021 Feb 17;116:105221. Epub 2021 Feb 17.

Department of Oral Pathology, University of Fortaleza / Universidade de Fortaleza, School of Dentistry, Fortaleza, Brazil.

Objective: To identify chromosome deletions in 1q25, 1p36 and 1pTEL, and chromosome 17 ploidy status in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC).

Material And Methods: Samples from 57 OED and 63 OSCC were selected. FISH was performed using centromeric probes 17 and n LSIR 1p36/LSI 1q25 Dual Color Probe.

Results: In OED, deletions were found only in 1pTEL region (29.8%). In OSCC, there was a higher frequency of deletion in 1pTEL (79.4%), followed by 1p36 (73.0%), and 1q25 (20.6%). Advanced TNM clinical stages (III/IV) showed all the deletions studied; at early clinical stages (I/II) of OSCC, deletions were observed only in 1pTEL. The frequency of deletion in 1p36 was 17.0 times higher in OSCC at advanced clinical stages (PR: 17.00). The median number of cell nuclei with chromosome 17 aneuploidy was higher in OSCC than in OED (P < 0.001). Early clinical stages of OSCC showed lower median number nuclei with aneuploidy when compared to advanced tumors (P < 0.05). Tumors harboring deletions in 1p36, 1q25 and 1pTEL revealed higher median numbers of trisomic/polysomic nuclei when compared to lesions exhibiting no abnormalities in chromosome 1 (P < 0.05).

Conclusion: A higher prevalence of chromosomal abnormalities was found in OSCC than in OED, while in OSCC, higher abnormalities were present in lesions with higher TNM staging. 1pTEL deletion and monosomy of chromosome 17 are possible markers for progression of OED to OSCC. 1p36 deletion and trisomy/polysomy of chromosome 17 could be markers of worse prognosis of OSCC.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105221DOI Listing
February 2021

Genetic Diversity of Drug-Related Genes in Native Americans of the Brazilian Amazon.

Pharmgenomics Pers Med 2021 22;14:117-133. Epub 2021 Jan 22.

Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, Brazil.

Introduction: The genetic admixture of the Brazilian population has considerable relevance to the implementation of the principles of pharmacogenomics (PGx), as it may compromise the extrapolation of data obtained in more homogeneous world populations.

Purpose: This study aims to investigate a panel of 117 polymorphisms in 35 pharmacogenes, which contains label recommendations or clinical evidence by international drug regulatory agencies, in Amazonian Native American populations, and compare the results obtained with continental population data from the 1000 Genomes Project Consortium.

Patients And Methods: The study population is composed of 109 Native American individuals from three Brazilian Amazon groups. The genotyping of the PGx polymorphisms was performed by allelic discrimination using TaqMan OpenArray Genotyping with a panel of 120 customized assays on the QuantStudio™ 12K Flex Real-Time PCR System.

Results: Statistical differences within the Native American populations were observed regarding both genotypes and phenotypes of some genes of the CYP family. The discriminant analysis of principal components (DAPCs) between the NAM group and the continental populations of the 1000 Genomes Project resulted in the clustering of the three Native American populations. Additionally, in general, the NAM group was determined to be closely situated between East Asia, America, and South Asia groups, which enabled us to infer a genetic similarity between these populations. The DAPC analysis further demonstrated that eight polymorphisms and six polymorphisms were more relevant in differentiating the NAM from the continental populations and the NAM populations among themselves, respectively.

Conclusion: Some investigated polymorphisms show differences among world populations, particularly with populations of European origin, for whom precision medicine protocols are primarily designed. The accumulated knowledge regarding these variations may assist in the design of specific protocols for Native American populations and populations admixed with them.
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http://dx.doi.org/10.2147/PGPM.S274741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837547PMC
January 2021

Identification of Variants (rs11571707, rs144848, and rs11571769) in the Gene Associated with Hereditary Breast Cancer in Indigenous Populations of the Brazilian Amazon.

Genes (Basel) 2021 Jan 22;12(2). Epub 2021 Jan 22.

Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66075-110, Brazil.

Estimates show that 5-10% of breast cancer cases are hereditary, caused by genetic variants in autosomal dominant genes; of these, 16% are due to germline mutations in the and genes. The comprehension of the mutation profile of these genes in the Brazilian population, particularly in Amazonian Amerindian groups, is scarce. We investigated fifteen polymorphisms in the and genes in Amazonian Amerindians and compared the results with the findings of global populations publicly available in the 1000 Genomes Project database. Our study shows that three variants (rs11571769, rs144848, and rs11571707) of the gene, commonly associated with hereditary breast cancer, had a significantly higher allele frequency in the Amazonian Amerindian individuals in comparison with the African, American, European, and Asian groups analyzed. These data outline the singular genetic profiles of the indigenous population from the Brazilian Amazon region. The knowledge about and variants is critical to establish public policies for hereditary breast cancer screening in Amerindian groups and populations admixed with them, such as the Brazilian population.
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http://dx.doi.org/10.3390/genes12020142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911168PMC
January 2021

Downregulated genes by silencing pathway identified with RNA-SEQ analysis as potential prognostic biomarkers in gastric adenocarcinoma.

Aging (Albany NY) 2020 12 22;12(24):24651-24670. Epub 2020 Dec 22.

Laboratory of Human Cytogenetics, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil.

overexpression is a common phenomenon in gastric carcinogenesis. In this study, we identified genes differentially expressed with a downregulated profile in gastric cancer (GC) cell lines with silenced MYC. The , , , , , genes were validated using qRT-PCR, western blot and immunohistochemistry in tissues of 213 patients with diffuse and intestinal GC. We identified high levels of , , , , associated with early and advanced stages, lymph nodes, distant metastases and risk factors such as H. pylori. Our results show that in the diffuse GC the overexpression of and indicate markers of poor prognosis higher than . That is, patients with overexpression of these two genes live less than patients with overexpression of . In the intestinal GC, patients who overexpressed CDC16 had a significantly lower survival rate than patients who overexpressed and , indicating in our data a worse prognostic value of compared to the other two genes. and proved to be important for assessing tumor progression in the early and advanced stages. In summary, in this study, we identified diagnostic and prognostic biomarkers of GC under the control of , related to the cell cycle and the neoplastic process.
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http://dx.doi.org/10.18632/aging.202260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803532PMC
December 2020

Significance of Expression and Loss of Heterozygosity in Human Papilloma Virus-related Oral Squamous Cell Carcinoma.

Anticancer Res 2020 Nov;40(11):6355-6366

Laboratory of Molecular Biology, Ophir Loyola Hospital, Belém, Brazil.

Background/aim: p16 and PTEN are tumor suppressor genes. Loss of these molecules in oral squamous cell carcinoma (OSCC) has been studied worldwide. In this study, we explored whether p16 cooperates with inactive PTEN during the pathogenesis of OSCC, especially in regard to tumor aggressiveness and proliferation.

Materials And Methods: Immunocytochemistry and western blot analysis were used to examine the levels of p16 and PTEN. Sequencing analysis was performed to identify mutations in the PTEN gene and HPV infection. Fluorescence in situ hybridization was used to examine the presence of the PTEN locus.

Results: PTEN analysis showed high positivity in T4 samples. HPV-positive tumors correlated with tabagism, tumor size 3 and 4, disease stages 3 and 4, presence of lymph node metastasis (N1) and poor differentiation. Immunoexpression of p16 was strongly correlated with the presence of HPV.

Conclusion: PTEN demonstrated a higher reactivity in advanced disease stages and p16 was strongly associated with HPV. Viral presence decreases tumor aggressiveness. Patients with advanced stage lesions demonstrated lower survival rate.
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http://dx.doi.org/10.21873/anticanres.14656DOI Listing
November 2020

Human pegivirus (HPgV, GBV-C) RNA in volunteer blood donors from a public hemotherapy service in Northern Brazil.

Virol J 2020 10 14;17(1):153. Epub 2020 Oct 14.

Center for Life Science and Health, Pará State University, Travessa. Perebebuí, 2623, Marco, Belém, Pará, 66087-662, Brazil.

Background: Human pegivirus (HPgV)-formerly known as GBV-C-is a member of the Flaviviridae family and belongs to the species Pegivirus C. It is a non-pathogenic virus and is transmitted among humans mainly through the exposure to contaminated blood and is often associated with human immunodeficiency virus (HIV) infection, among other viruses. This study aimed to determine the prevalence of HPgV viremia, its association with HIV and clinical epidemiological factors, as well as the full-length sequencing and genome characterization of HPgV recovered from blood donors of the HEMOPA Foundation in Belém-PA-Brazil.

Methods: Plasma samples were obtained from 459 donors, tested for the presence of HPgV RNA by the RT-qPCR. From these, a total of 26 RT-qPCR positive samples were submitted to the NGS sequencing approach in order to obtain the full genome. Genome characterization and phylogenetic analysis were conducted.

Results: The prevalence of HPgV was 12.42%. We observed the highest prevalences among donors aged between 18 and 30 years old (16.5%), with brown skin color (13.2%) and men (15.8%). The newly diagnosed HIV-1 prevalence was 26.67%. The HPgV genotype 2 (2a and 2b) was identified. No data on viral load value was found to corroborate the protective effect of HPgV on HIV evolution.

Conclusions: This study provided information regarding the HPgV infection among blood donors from HEMOPA Foundation. Furthermore, we genetically characterized the HPgV circulating strains and described by the first time nearly complete genomes of genotype 2 in Brazilian Amazon.
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http://dx.doi.org/10.1186/s12985-020-01427-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556973PMC
October 2020

Computational Identification and Characterization of New microRNAs in Human Platelets Stored in a Blood Bank.

Biomolecules 2020 08 12;10(8). Epub 2020 Aug 12.

Laboratory of Human Cytogenetics, Institute of Biological Sciences, Federal University of Pará, Belém, PA 66075-110, Brazil.

Platelet concentrate (PC) transfusions are widely used to save the lives of patients who experience acute blood loss. MicroRNAs (miRNAs) comprise a class of molecules with a biological role which is relevant to the understanding of storage lesions in blood banks. We used a new approach to identify miRNAs in normal human platelet sRNA-Seq data from the GSE61856 repository. We identified a comprehensive miRNA expression profile, where we detected 20 of these transcripts potentially expressed in PCs stored for seven days, which had their expression levels analyzed with simulations of computational biology. Our results identified a new collection of miRNAs (miR-486-5p, miR-92a-3p, miR-103a-3p, miR-151a-3p, miR-181a-5p, and miR-221-3p) that showed a sensitivity expression pattern due to biological platelet changes during storage, confirmed by additional quantitative real-time polymerase chain reaction (qPCR) validation on 100 PC units from 500 healthy donors. We also identified that these miRNAs could transfer regulatory information on platelets, such as members of the let-7 family, by regulating the gene, which is a deubiquitinating enzyme highly expressed in platelet hyperactivity. Our results also showed that the target genes of these miRNAs play important roles in signaling pathways, cell cycle, stress response, platelet activation and cancer. In summary, the miRNAs described in this study, have a promising application in transfusion medicine as potential biomarkers to also measure the quality and viability of the PC during storage in blood banks.
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http://dx.doi.org/10.3390/biom10081173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464399PMC
August 2020

Helicobacter pylori cagE, cagG, and cagM can be a prognostic marker for intestinal and diffuse gastric cancer.

Infect Genet Evol 2020 Oct 29;84:104477. Epub 2020 Jul 29.

Department of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address:

It is known that Helicobacter pylori is the main cause of peptic ulceration and gastric cancer. However, there is a lack of information on whether H. pylori strains may differ in gastric cancer histological subtypes. This study aimed to investigate different H. pylori strains considering six cag Pathogenicity Island - cagPAI genes (cagA, cagE, cagG, cagM, cagT, and virb11), and vacuolating cytotoxin - vacA alleles, and their relation to gastric cancer histologic subtypes. For this purpose, tumor samples from 285 patients with gastric carcinoma were used. H. pylori infection and genotypes were determined by polymerase chain reaction (PCR). H. pylori was detected in 93.9% of gastric tumors. For comparative analyzes between histopathological subtypes considering H. pylori cagPAI genes the strains were grouped according to the vacA s1/s2 alleles. In the vacAs1 group, the strains cagA(-)cagE(+), cagA(+)cagE(+)cagG(+), cagA(+)cagM(+), or only cagE(+) strains were more frequent in the intestinal subtype (P = .009; P = .024; P = .046, respectively). In contrast, cagM(+)cagG(+)cagA(-) and cagE(-) were associated with diffuse tumors (P = .036), highlighting the presence of cagE in the development of intestinal tumors, and the presence of cagG and absence of cagE in diffuse tumors. Furthermore, WEKA software and Decision Tree (CART) analyses confirmed these findings, in which cagE presence was associated with intestinal tumors, and cagE absence and cagG(+) with diffuse tumors. In conclusion our results showed that vacAs1 (cagG + cagM) strains, mainly cagG positive with cagE absence, were relevant in the studied population for the diffuse outcome, while the presence of cagE was relevant for the intestinal outcome. These findings suggest the relevance of these H. pylori genes as potential markers for gastric cancer histological outcomes.
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http://dx.doi.org/10.1016/j.meegid.2020.104477DOI Listing
October 2020

MicroRNAs as a Potential Quality Measurement Tool of Platelet Concentrate Stored in Blood Banks-A Review.

Cells 2019 10 15;8(10). Epub 2019 Oct 15.

Laboratory of Human Cytogenetics, Institute of Biological Sciences, Federal University of Pará, Belém, PA 66075-110, Brazil.

Background: Platelet concentrate (PC) is one of the main products used in a therapeutic transfusion. This blood component requires special storage at blood banks, however, even under good storage conditions, modifications or degradations may occur and are known as platelet storage lesions.

Methods: This research was performed on scientific citation databases PubMed/Medline, ScienceDirect, and Web of Science, for publications containing platelet storage lesions. The results obtained mainly reveal the clinical applicability of miRNAs as biomarkers of storage injury and as useful tools for a problem affecting public and private health, the lack of PC bags in countries with few blood donors. The major studies listed in this review identified miRNAs associated with important platelet functions that are relevant in clinical practice as quality biomarkers of PC, such as miR-223, miR-126, miR-10a, miR-150, miR-16, miR-21, miR-326, miR-495, let-7b, let-7c, let-7e, miR-107, miR-10b, miR-145, miR-155, miR-17, miR-191, miR-197, miR-200b, miR-24, miR-331, miR-376. These miRNAs can be used in blood banks to identify platelet injury in PC bags.

Conclusion: The studies described in this review relate the functions of miRNAs with molecular mechanisms that result in functional platelet differences, such as apoptosis. Thus, miRNA profiles can be used to measure the quality of storage PC for more than 5 days, identify bags with platelet injury, and distinguish those with functional platelets.
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http://dx.doi.org/10.3390/cells8101256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829606PMC
October 2019

Epigenetic Field Cancerization in Gastric Cancer: microRNAs as Promising Biomarkers.

J Cancer 2019 26;10(6):1560-1569. Epub 2019 Feb 26.

Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa Avenue, 66075-110, Belém, Pará, Brazil.

The biological role of microRNAs (miRNAs) in field cancerization is unknown. To investigate the involvement of miRNAs in gastric field cancerization, we evaluated the expression profile of ten miRNAs and their diagnostic value. We used three groups of FFPE gastric samples: non-cancer (NC), cancer adjacent (ADJ) and gastric cancer (GC). The expression profiles of , , , , , , and were investigated using qRT-PCR. The results obtained by qRT-PCR were validated in Small RNA-Seq data from the TCGA database. The search for target genes of the studied miRNAs was performed in the miRTarBase public database and miRTargetLink tool, using experimentally validated interactions. In addition, we also performed the functional analysis of these genes using enrichment in KEGG pathways. The potential as biomarker was evaluated using a receiver operating characteristic (ROC) curve and the derived area under the curve (AUC>0.85) analysis. The miRNAs , , , , , , , and were up-regulated in ADJ and GC compared to NC (<0.03); and and were up-regulated in GC compared to ADJ (<0.01). , , , and were not differentially expressed between GC and ADJ, suggesting that both share similar changes (>0.1). The TS-miR was up-regulated in ADJ compared to NC and GC (<0.01); we did not observe a significant difference in the expression of this miRNA between NC and GC. This feature may be an antitumor mechanism used by cancer-adjacent tissue because this miRNA regulates the , and oncogenes. The expression level of was associated with infection status (<0.05) Functional analysis using the genes regulated by the studied miRNAs showed that they are involved in biological pathways and cellular processes that are critical for the establishment of infection and for the onset, development and progression of GC. , , , , , , and were able to discriminate NC from other tissues with great accuracy (AUC>0.85). The studied miRNAs are closely related to field cancerization, regulate genes important for gastric carcinogenesis and can be potentially useful as biomarkers in GC.
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http://dx.doi.org/10.7150/jca.27457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485221PMC
February 2019

Effect of the kaurenoic acid on genotoxicity and cell cycle progression in cervical cancer cells lines.

Toxicol In Vitro 2019 Jun 27;57:126-131. Epub 2019 Feb 27.

Federal Institute of Education, Science and Technology of Pará (IFPA), Belém, PA, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.tiv.2019.02.022DOI Listing
June 2019

Traps and trumps from adjacent-to-tumor samples in gastric cancer research.

Chin J Cancer Res 2018 Oct;30(5):564-567

Laboratory of Molecular Biology, Ophir Loyola Hospital, Belém 66060-281, Brazil.

The search for cancer biomarkers is frequently based on comparisons between tumors and adjacent-to-tumor samples. However, even after histological confirmation of been free of cancer cells, these adjacent-to-tumor samples might harbor molecular alterations which are not sufficient to cause them to look like cancer, but can differentiate these cells from normal cells. When comparing them, potential biomarkers are missed, and mainly the opportunity of finding initial aberrations presents in both tumors and adjacent samples, but not in true normal samples from non-cancer patients, resulting in misinterpretations about the carcinogenic process. Nevertheless, collecting adjacent-to-tumor samples brings trumps to be explored. The addition of samples from non-cancer patients opens an opportunity to increase the finds of the molecular cascade of events in the carcinogenic process. Differences between normal samples and adjacent samples might represent the first steps of the carcinogenic process. Adding samples of non-cancer patients to the analysis of molecular alterations relevant to the carcinogenic process opens a new window of opportunities to the discovery of cancer biomarkers and molecular targets.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2018.05.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232362PMC
October 2018

Association between , Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas.

World J Gastroenterol 2018 Nov;24(43):4928-4938

Laboratory of Human Cytogenetics, Institute of Biological Sciences, Federal University of Pará, Belém, Pará 66075-110, Brazil.

Aim: To correlate (), Epstein-Barr virus (EBV) and human papillomavirus (HPV) with gastric cancer (GC) cases in Pará State, Brazil.

Methods: Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of , and the presence of the gene in the HP-positive samples was confirmed by PCR. An RNA hybridization test designed to complement Eber1 RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.

Results: The majority of the 302 samples analyzed were obtained from men (65%) aged 55 years or older (67%) and were classified as the intestinal subtype (55%). All three pathogens were found in the samples analyzed in the present study (: 87%, EBV: 20%, HPV: 3%). Overall, 78% of the -positive () samples were + (-), and there was an association between the cytotoxic product of this gene and EBV. Coinfections of - and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.

Conclusion: HPV was not involved in gastric tumorigenesis. Prophylactic and therapeutic measures against and EBV may prevent the development of GC, especially the more aggressive forms.
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http://dx.doi.org/10.3748/wjg.v24.i43.4928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250917PMC
November 2018

Differential Expression Profile of MicroRNAs During Prolonged Storage of Platelet Concentrates As a Quality Measurement Tool in Blood Banks.

OMICS 2018 10 27;22(10):653-664. Epub 2018 Sep 27.

3 Laboratory of Molecular Biology, Ophir Loyola Hospital , Belém, Brazil .

Platelet concentrate (PC) is a key blood component, which even in good storage conditions, susceptible to cellular damage over time. Hence, blood banks discard unused PC bags after 5 days of storage. Biomarkers of PC quality are therefore highly sought after in blood bank governance. We used the data (Gene Expression Omnibus: GSE61856) generated with next-generation sequencing to examine the expression profiles of microRNAs (miRNAs) from PCs that were stored for 6 days in a blood bank, that is, 1 day longer than is normally stored PC. We identified the 14 most differentially expressed miRNAs by comparing a control PC on the first day of storage with the PCs on each of the subsequent 5 days of storage from day 1 to 6. In all, we identified nine miRNAs with the downregulated profile (miR-145-5p, miR-150-5p, miR-183-5p, miR-26a-5p, miR-331-3p, miR-338-5p, miR-451a, miR-501-3p, and miR-99b-5p) and five upregulated miRNAs (miR-1304-3p, miR-411-5p, miR-432-5p, miR-668-3p, and miR-939-5p). These miRNAs were validated by real-time quantitative PCR in 100 PC units. As each PC unit is composed of platelets of five individuals, the validation was thus performed in 500 individuals (250 men and 250 women, comprised 18-40 years old adults). The data were analyzed with hierarchical clustering and principal component analysis, which revealed the variation of mean relative expression and the instability of miRNAs half-life on the fourth day of PC storage, which coincides with time of onset of platelet storage lesions. These new observations can usefully inform future decision-making and governance in blood banks concerning PC quality.
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http://dx.doi.org/10.1089/omi.2018.0126DOI Listing
October 2018

Small benzothiazole molecule induces apoptosis and prevents metastasis through DNA interaction and c-MYC gene supression in diffuse-type gastric adenocarcinoma cell line.

Chem Biol Interact 2018 Oct 11;294:118-127. Epub 2018 Aug 11.

Drug Research and Development Center (NPDM), Federal University of Ceará - Rua Cel, Nunes de Melo, n.1000 - Rodolfo Teófilo, Fortaleza, CE, Brazil; Biological Science Institute, Federal University of Pará - Rua Augusto Correa, n.01 - Guamá, Belem, Pará, Brazil. Electronic address:

Chemo-resistance has been reported as a relevant barrier for the efficiency of gastric cancer treatment. Therefore, the development of effective and safe drugs for cancer chemotherapy is still a challenge. The purpose of this study was to evaluate the anticancer potential of (E)-2-(((2-(benzo[d]thiazo-2-yl)hydrazono)methyl)-4-nitrophenol) (AFN01) against gastric cancer cell lines. Our results showed promising anticancer activity against gastric cancer cells ACP-02 (IC = 1.0 μM) and mild activity against other cell lines including non-malignant gastric cell MNP-01 (IC = 3.4 μM). This compound significantly induced S phase cell cycle arrest, prevented cell migration and triggered apoptosis in a concentration-dependent manner. Moreover, AFN01 was significantly more genotoxic against tumoral cell ACP-02, when compared to non-malignant cells, such as MNP-01 and healthy peripheral mononuclear blood cells. AFN01 also synergistically interacts with doxorubicin suppressing cell proliferation and c-MYC gene expression in gastric cancer cell line model, with remarkable c-MYC overexpression. Although further pre-clinical and clinical studies are required to explore its safety and efficiency, AFN01 may represent a promising lead anticancer agent for the treatment of gastric cancer.
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http://dx.doi.org/10.1016/j.cbi.2018.08.006DOI Listing
October 2018

Mutagenic and histopathological effects of hexavalent chromium in tadpoles of Lithobates catesbeianus (Shaw, 1802) (Anura, Ranidae).

Ecotoxicol Environ Saf 2018 Nov 29;163:400-407. Epub 2018 Jul 29.

Fishery and Agribusiness Resource Coordination (Coordenação de Recursos Pesqueiros e Agronegócio), Federal Institute of Education, Science and Technology of Pará (Instituto Federal de Educação, Ciência e Tecnologia do Pará), Belém, Pará, Brazil. Electronic address:

The potential mutagenic and histopathological effects of the hexavalent chromium were investigated in Lithobates catesbeianus tadpoles. These larvae (GS 25-31) were exposed to three nominal concentrations of potassium dichromate (4, 12, and 36 mg L) and 5 mg L of Cyclophosphamide as a positive control (PC), for 24 h. A negative control (NC) was also added to the experiment. Our results showed that, in general, the micronuclei (MN) were less frequent than the erythrocyte nuclear abnormalities (ENA); there was a significant difference in the frequency of MN between the NC and all treated groups (p < 0.05) in a concentration-dependent curve, in addition the PC did not differ from the chromium treatments. Also, only PC and the group treated with potassium dichromate at 36 mg L showed significantly higher frequencies of ENA than NC (p < 0.05). Chromium treatments promoted cell retention in the Sub-G1 phase and a decrease of cells in the S and G2/M phases indicating inhibition of the cell cycle. All treatments with chromium led to liver and kidney histopathological lesions, especially with 36 mg L (greater number of lesions). In conclusion, hexavalent chromium was mutagenic to L. catesbeianus tadpoles and its toxic effects also resulted in anti-mitotic activity, besides inducing histopathological alterations in liver and kidney. Amphibians have been proven to be useful bioindicators, and we suggest that tadpoles of different species can be used to represent the environmental impacts in aquatic ecosystems.
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http://dx.doi.org/10.1016/j.ecoenv.2018.07.083DOI Listing
November 2018

COX-2 gene expression and methylation profile in Sapajus apella as an experimental model for gastric adenocarcinoma.

Genet Mol Biol 2018 Apr./Jun;41(2):496-501. Epub 2018 May 14.

Molecular Biology Laboratory, Instituto de Ciências Biológicas. Universidade Federal do Pará, Belém, PA, Brazil.

Gastric cancer (GC) remains one of the main causes of cancer-related death worldwide. There are two distinct histological types of GC: diffuse and intestinal. The latter is characterized by the presence of pre-neoplastic lesions. One of the most frequently altered enzymes in intestinal GC is COX-2, an important lesion marker. This work aimed to study COX-2 methylation and expression in N-methyl-N-Nitrosurea (MNU)-induced intestinal GC in six Sapajus apella animals. The partial promoter sequence of S. apella COX-2 gene was obtained and used to identify transcription factors and cis-regulatory element binding sites. The COX-2 methylation pattern was assessed using Methylation-Specific PCR (MSP), and expression was analyzed by immunohistochemistry (IHQ). A total of 20 samples were obtained. A 675 bp fragment of the S. apella COX-2 promoter region was obtained, and it was 99.2% and 68.2% similar to H. sapiens and S. boliviensis, respectively. Similar to humans, several transcription factors and cis-regulatory element binding sites were identified in the S. apella sequence. MSP revealed that all samples were methylated. However, IHQ results demonstrated positive COX-2 expression in all pre-neoplastic and tumoral samples. The results suggest that the analyzed fragment is not crucial in COX-2 regulation of GC in S. apella.
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http://dx.doi.org/10.1590/1678-4685-GMB-2016-0329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082229PMC
May 2018

The potential European genetic predisposition for non-contact anterior cruciate ligament injury.

Knee Surg Sports Traumatol Arthrosc 2018 Dec 4;26(12):3532-3536. Epub 2018 May 4.

Centro de Traumatologia do Esporte, Orthopaedic Surgeon from Universidade Federal de São Paulo, Av Pacaembu 1024, São Paulo, SP, 01234-000, Brazil.

Purpose: Previous research has provided evidence of a hereditary predisposition for anterior cruciate ligament (ACL) injury. The purpose of this study was to evaluate the association between ancestral population genetics and risk of non-contact ACL injuries.

Methods: Blood samples were collected from 177 individuals with a history of non-contact ACL injury and 556 non-injured control individuals for analysis of the genetic material through the use of a panel of 48 INDELs ancestry genetic markers from three ancestral origins.

Results: Among patients with non-contact ACL injury, 82% were male and 18% were female. In the control group, 78% were male, and 22% were female. The mean age of the non-contact ACL injury group was 31.7 years (± 10.2), and the control group was 33.8 years (± 13.2). The individual genetic contribution from INDELs of each ancestral origin varied considerably: ranging between 1.5-94.8% contribution for INDELs of African origin (mean of 21.4% of INDELs); between 2 and 96.1% contribution for INDELs of European origin (mean of 66.7% of INDELs); and between 1.3-96.4% contribution for INDELs of Amerindian origin (mean of 11.7% of INDELs). When comparing paired subjects from the non-contact ACL and control groups, the genetic analysis showed that the European ancestry score was higher in the non-contact ACL group than control group (0.70 ± 0.21 vs 0.63 ± 0.22 respectively, p < 0.001), whereas African ancestry scores (ACL group 0.18 ± 0.18 vs control group 0.24 ± 0.21, p < 0.001) and Amerindian ancestry scores (ACL group 0.11 ± 0.09 vs control group 0.12 ± 0.10, n.s.) were lower among the non-contact ACL group than in controls.

Conclusion: European INDELs markers were found to represent a potential genetic predisposition for non-contact ACL injuries when compared to African and Amerindian INDELs. This study has the potential to correlate a measurable and distinct genetic marker with risk of a non-contact ACL injury. Thus, it increases knowledge base and volume of molecular and genetical factors associated with this pathology. Furthermore, this study provides guidance and evidence for the development of genetic risk-screening panels for non-contact ACL injury.

Level Of Evidence: Level III Diagnostic Study.
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http://dx.doi.org/10.1007/s00167-018-4974-7DOI Listing
December 2018

HPV positive, wild type TP53, and p16 overexpression correlate with the absence of residual tumors after chemoradiotherapy in anal squamous cell carcinoma.

BMC Gastroenterol 2018 Feb 21;18(1):30. Epub 2018 Feb 21.

Hospital Ophir Loyola, Belém, Pará, 66060-281, Brazil.

Background: Anal residual tumors are consensually identified within six months of chemoradiotherapy and represent a persistent lesion that may have prognostic value for overall survival. The aim of this study was to evaluate the association of HPV and HIV status, p16 expression level and TP53 mutations with the absence of residual tumors (local response) in Squamous Cell Carcinoma (SCC) of the anal canal after chemoradiotherapy.

Methods: We performed a study on 78 patients with SCC of the anal canal who submitted to chemoradiotherapy and were followed for a six-month period to identify the absence or presence of residual tumors. HPV DNA was identified by polymerase chain reaction and direct sequencing, HIV RNA was detected by TaqMan amplification, p16 expression was detected by western blotting, and the mutational analysis of TP53 was performed by direct sequencing; additionally, samples carrying mutations underwent fluorescent in sit hybridization. The evaluation of the tumor response to treatment was conducted six months after the conclusion of chemoradiotherapy. The following classifications were used to evaluate the outcomes: a) no response (presence of residual tumor) and b) complete response (absence of residual tumor).

Results: The significant variables associated with the absence of residual tumors were HPV positive, p16 overexpressed, wild-type TP53, female gender, and stages I and II. Only the presence of HPV was independently correlated with the clinical response; this variable increased the chances of a response within six months by 31-fold.

Conclusions: The presence of HPV in tumor cells was correlated with the absence of a residual tumor. This correlation is valuable and can direct future therapeutic approaches in the anal canal.
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http://dx.doi.org/10.1186/s12876-018-0758-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822520PMC
February 2018

GEJ cancers: gastric or esophageal tumors? searching for the answer according to molecular identity.

Oncotarget 2017 Nov 31;8(61):104286-104294. Epub 2017 Oct 31.

Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil.

The 7th edition of Union for International Cancer Control (UICC) staging system moved gastroesophageal junction (GEJ) cancers from gastric to esophageal group. Since clinical management is strongly influenced by this staging system, we looked at molecular fingerprints of GEJ tumors and compared to gastric and esophageal profiles. We aimed at elucidating whether GEJ cancers cluster with gastric or esophageal groups according to mRNA and microRNA expression pattern, since this might represent tumor identity. The clinical and expression data were downloaded from The Cancer Genome Atlas (TCGA) with 395 stomach, 184 esophagus and 521 colon samples for mRNA analyses and 392 stomach, 175 esophagus and 459 colon samples for microRNA comparisons. Both Principal Component Analysis (PCA) and Heat Map plots were performed in R platform, using Log transformation of RPKM normalized data. Differential Expression Analysis was also performed in R, using RAW data and the DESeq2 package. The mRNAs and microRNAs were tagged as differentially expressed if they met the following criteria: i) FDR adjusted p-value < 0.05; and ii) |Log (fold-change)| > 2. Esophagus squamous cell carcinoma (ESCC) clustered apart of the others tumors, while adenocarcinomas (AC) clustered all together according to both mRNAs and microRNAs expression patterns. The HMs of the differentially expressed mRNAs and microRNAs also demonstrated that ESCC belongs to a different group, while AC molecular signature of esophagus looks like AC of the cardia and non cardia regions. Even distal gastric cancers are quite similar to AC of the lower esophagus, demonstrating that esophagus AC relies much closer to gastric cancers than to esophagus cancers. By using robust molecular fingerprints, it was strongly demonstrated that GEJ tumors looks more like gastric cancers than esophageal cancers, despite of tumor heterogeneity.
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http://dx.doi.org/10.18632/oncotarget.22216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732806PMC
November 2017

Role for apolipoprotein E in neurodegeneration and mercury intoxication.

Front Biosci (Elite Ed) 2018 Jan 1;10:229-241. Epub 2018 Jan 1.

Laboratorio de Farmacologia Molecular, Instituto de Ciencias Biologicas (ICB), Universidade Federal do Para (UFPA), Belem, Brazil,

Mercury intoxication is a serious public health problem and a worldwide concern. The Minamata Convention on Mercury has been signed by 128 countries and endorsed by the World Health Organization with the recommendation of promoting the management of epidemiological information. The Central Nervous System is the main target organ for mercury. Symptoms of intoxication include altered motor coordination, visual and tactile dysfunction and paralysis, caused by neurodegeneration with a key role for oxidative damage. Recently, some studies have demonstrated a correlation between mercury intoxication and isoforms of apolipoprotein E (ApoE). In this review, epidemiological data and hypotheses about the possible molecular mechanisms underlying the association between ApoE and mercury intoxication are assessed. Based on the evidence and the neuropathological changes that the presence of ApoE4 and mercury neurotoxicity have in common, we propose a convergent action of both factors. ApoE4 seems to potentiate the damage caused by mercury. Increased knowledge of this interaction using epidemiological and pre-clinical studies is essential to improve prevention strategies to adequately manage intoxicated patients.
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http://dx.doi.org/10.2741/e819DOI Listing
January 2018

The intricate interplay between MSI and polymorphisms of DNA repair enzymes in gastric cancer H.pylori associated.

Mutagenesis 2017 07;32(4):471-478

Laboratory of Molecular Genectic, Department of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.

Gastric cancer is the fourth most common type of cancer worldwide. Helicobacter pylori is a well-established risk factor and may cause injuries to genomic integrity through an inefficient DNA repair. This study aimed to examine the influence of polymorphisms in DNA repair enzymes using markers for microsatellite instability (MSI). Polymorphisms of DNA repair enzymes were detected by PCR-RFLP and MSI, by high resolution melt (HRM) analysis. Helicobacter pylori detection and genotyping were accomplished by PCR. MSI was observed in 47.5% of the cases and it was associated with the ERCC1 polymorphic allele, whereas MSI-H was associated with the XRCC3 heterozygous genotype. MSI was more frequent in intestinal gastric cancer (IGC), where it was associated with ERCC1 or RAD51 polymorphic alleles. Also, MSI-H was associated with the XRCC3 heterozygous. In diffuse gastric cancer (DGC), almost all of MGMT polymorphic genotype carriers showed MSI. Helicobacter pylori was positive in 94% of the cases and the most virulent strains were associated with MSI, mainly MSI-H. When the subtypes were considered, these associations were found only in the IGC and associated with more virulent strains. Among the cases with microsatellite instability, IGC showed a correlation between the XPD wild-type and the ERCC1 polymorphic allele, and all of them were infected by the most virulent strains. On the other hand, in DGC, the XPD polymorphic allele was correlated with the XRCC3 wild-type with no prevalence of H.pylori virulence. Our data demonstrated that polymorphisms in repair enzymes can interfere with the efficiency of the repair process, but it differs depending on the histological subtype and H.pylori involvement. Besides nucleotide excision repair, base excision repair and mismatch repair pathway, the homologous recombination are also involved.
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http://dx.doi.org/10.1093/mutage/gex013DOI Listing
July 2017

Mebendazole, an antiparasitic drug, inhibits drug transporters expression in preclinical model of gastric peritoneal carcinomatosis.

Toxicol In Vitro 2017 Sep 9;43:87-91. Epub 2017 Jun 9.

Biological Science Institute, Federal University of Para, Belem, Pará, Brazil; Laboratory of Pharmacogenomics, Nucleus of Research and Development of Medicines (NPDM), Federal University of Ceara, Fortaleza, Ceará, Brazil. Electronic address:

The present study aimed to investigate whether MBZ down-regulates drug transporter expression (ABCB1, ABCC1, SLC47A1). mRNA expression level of ABCB1, ABCC1 and SLC47A1 was evaluated by qPCR and protein expression levels MDR-1 was performed by western blotting in malignant ascites cells (AGP-01) treated with MBZ for 24h. The mRNA expression level of ABCB1 and ABCC1 significantly decreased at a 1.0μM of MBZ compared to negative control, while SLC47A1 extremely decreased at all tested concentrations of MBZ. Protein expression levels MDR-1 significantly decreased at a 1.0μM of MBZ compared to negative control. Therefore, our results showed MBZ may play an important role in inhibiting MDR gene expression in malignant ascites cells.
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http://dx.doi.org/10.1016/j.tiv.2017.06.007DOI Listing
September 2017

Residual risk of transmission of human immunodeficiency virus and hepatitis C virus infections by blood transfusion in northern Brazil.

Transfusion 2017 08 7;57(8):1968-1976. Epub 2017 Jun 7.

Laboratory of Genetics and Molecular Biology, Foundation Center for Hemotherapy and Hematology of Pará (HEMOPA).

Background: Nucleic acid test (NAT) blood screening for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) was introduced in northern Brazil in July 2012. There are several Brazilian articles that have evaluated transfusion transmission risks for HIV and HCV. However, to our knowledge, this article is the first to evaluate the impact of HIV and HCV NAT implementation for blood screening in northern Brazil. The aim of this study was to determine the prevalence and incidence rates of HIV and HCV among blood donors and to compare the residual risk of transfusion transmission of these infections, before (2009-2011) and after (2012-2014) NAT implementation.

Study Design And Methods: HIV and HCV prevalence and incidence were calculated based on rates of confirmed positive samples. Residual risk estimates were based on the incidence and window model described previously. Logistic and Poisson regressions were used in the statistical analysis. A p value of not more than 0.05 was considered significant.

Results: HIV and HCV prevalence were 209.9 and 66.3 per 100,000 donations, respectively. Residual risk for HIV and HCV decreased significantly throughout the two study periods, mainly for HCV in which the reduction was one in 169,492 to one in 769,231 donations. For HIV, the decrease was one in 107,527 to one in 769,231 donations. HIV and HCV incidence rates were 21.13 and 3.06 per 100,000 persons/year before NAT and 14.03 and 2.65 per 100,000 persons/year after NAT.

Conclusion: The HIV and HCV NAT implementation significantly increased the transfusion safety in northern Brazil, bringing benefits to recipients due to better quality of blood products produced.
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http://dx.doi.org/10.1111/trf.14146DOI Listing
August 2017

Effect of diterpenoid kaurenoic acid on genotoxicity and cell cycle progression in gastric cancer cell lines.

Biomed Pharmacother 2017 May 6;89:772-780. Epub 2017 Mar 6.

Human Cytogenetic Laboratory, Biological Science Institute, Federal University of Pará (UFPA), Belém, Pará, Brazil; Hospital Ophir Loyola (HOL), Belém, Pará, Brazil. Electronic address:

The goal of our study was to evaluate the effect of kaurenoic acid, obtained from copaiba oil resin, in gastric cancer (GC) and a normal mucosa of stomach (MNP01) cell lines. The compound was tested at concentrations of 2.5, 5, 10, 30 and 60μg/mL. Comet and micronucleus assays were used to access its potential genotoxicity in vitro. Moreover, we evaluated the effect of kaurenoic acid in cell cycle progression and in the transcription of genes involved in the control of the cell cycle: MYC, CCND1, BCL2, CASP3, ATM, CHK2 and TP53. Kaurenoic acid induced an increase on cell DNA damage or micronucleus frequencies on GC cell lines in a dose-dependent manner. The GC and MNP01 cell lines entering DNA synthesis and mitosis decreased significantly with kaurenoic acid treatment, and had an increased growth phase compared with non-treated cells. The treatment induced apoptosis (or necrosis) even at a concentration of 2.5μg/mL in relation to non-treated cells. GC cell lines presented reduced MYC, CCND1, BCL2 and CASP3 transcription while ATM, CHK2 and TP53 increased in transcription in relation to non-treated cells, especially at a concentration above 10μg/mL. The gene transcription in the MNP01 (non-treated non-cancer cell line) was designated as a calibrator for all the GC cell lines. In conclusion, our results showed that kaurenoic acid obtained from Copaifera induces DNA damage and increases the micronuclei frequency in a dose-dependent manner in GC cells, with a significant genotoxicity observed above the concentration of 5μg/mL. Moreover, this compound seems to be able to induce cell cycle arrest and apoptosis in GC cells.
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http://dx.doi.org/10.1016/j.biopha.2017.02.085DOI Listing
May 2017

Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer.

World J Gastroenterol 2016 Sep;22(35):7951-62

Kelly Cristina da Silva Oliveira, Taíssa Maíra Thomaz Araújo, Camila Inagaki Albuquerque, Gabriela Alcantara Barata, Fernando Augusto Rodrigues Mello Junior, André Salim Khayat, Paulo Pimentel de Assumpção, Danielle Queiroz Calcagno, Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Hospital Universitário João de Barros Barreto, Belém, PA 66073-000, Brazil.

Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on miRNA activity.
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http://dx.doi.org/10.3748/wjg.v22.i35.7951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028809PMC
September 2016

The anthelmintic drug mebendazole inhibits growth, migration and invasion in gastric cancer cell model.

Toxicol In Vitro 2015 Dec 24;29(8):2038-44. Epub 2015 Aug 24.

Biological Science Institute, Federal University of Para, Augusto Correa Avenue, 01 Guamá, Belém, Pará, Brazil. Electronic address:

The present study aimed to investigate the effects of MBZ on a human malignant ascites cell line derived from a primary gastric cancer tumor. Our data reveal that MBZ showed high cytotoxicity in vitro, displaying an IC50 of 0.39 μM and 1.25 μM in ACP-02 and ACP-03, respectively. The association between MBZ and 5-FU increased slightly the cytotoxicity when compared to MBZ and 5-FU alone. Furthermore, MBZ disrupted the microtubule structure of AGP-01 cells and inhibited significantly the invasion and migration of these cells. Activity of active MMP-2 significantly decreased at all tested concentration of MBZ compared to negative control. These results support the indication of MBZ in combination with chemotherapeutic agents as a possible adjuvant therapy for the management/treatment of patients with advanced gastric cancer since MBZ is a drug of low cost with acceptable safety profile and reduced toxicity to normal cells. However, clinical trials must be performed in o to evaluate its efficacy in gastric cancer patients.
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http://dx.doi.org/10.1016/j.tiv.2015.08.007DOI Listing
December 2015

The miRNA Profile of Platelets Stored in a Blood Bank and Its Relation to Cellular Damage from Storage.

PLoS One 2015 29;10(6):e0129399. Epub 2015 Jun 29.

Laboratory of Human Cytogenetics, Institute of Biological Sciences, Federal University of Pará, Belém, PA, 66075110, Brazil.

Millions of blood products are transfused each year, and many lives are directly affected by transfusion. Platelet concentrate (PC) is one of the main products derived from blood. Even under good storage conditions, PC is likely to suffer cell damage. The shape of platelets changes after 5 to 7 days of storage at 22°C. Taking into consideration that some platelet proteins undergo changes in their shape and functionality during PC storage. Sixteen PC bags were collected and each PC bag tube was cut into six equal pieces to perform experiments with platelets from six different days of storage. Thus, on the first day of storage, 1/6 of the tube was used for miRNA extraction, and the remaining 5/6 was stored under the same conditions until extraction of miRNAs on each the following five days. Samples were sequenced on an Illumina Platform to demonstrate the most highly expressed miRNAs. Three miRNAs, mir127, mir191 and mir320a were validated by real-time quantitative PCR (RQ-PCR) in 100 PC bags tubes. Our method suggests, the use of the miRNAs mir127 and mir320a as biomarkers to assess the "validity period" of PC bags stored in blood banks for long periods. Thus, bags can be tested on the 5th day of storage for the relative expression levels of mir127 and mir320a. Thus, we highlight candidate miRNAs as biomarkers of storage damage that can be used as tools to evaluate the quality of stored PC. The use of miRNAs as biomarkers of damage is unprecedented and will contribute to improved quality of blood products for transfusions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129399PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486185PMC
March 2016