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1.
Pediatr Cardiol ; 45(1): 165-174, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37932525

RESUMEN

This study aims to evaluate the feasibility and utility of virtual reality (VR) for baffle planning in congenital heart disease (CHD), specifically by creating patient-specific 3D heart models and assessing a user-friendly VR interface. Patient-specific 3D heart models were created using high-resolution imaging data and a VR interface was developed for baffle planning. The process of model creation and the VR interface were assessed for their feasibility, usability, and clinical relevance. Collaborative and interactive planning within the VR space were also explored. The study findings demonstrate the feasibility and usefulness of VR in baffle planning for CHD. Patient-specific 3D heart models generated from imaging data provided valuable insights into complex spatial relationships. The developed VR interface allowed clinicians to interact with the models, simulate different baffle configurations, and assess their impact on blood flow. The VR space's collaborative and interactive planning enhanced the baffle planning process. This study highlights the potential of VR as a valuable tool in baffle planning for CHD. The findings demonstrate the feasibility of using patient-specific 3D heart models and a user-friendly VR interface to enhance surgical planning and patient outcomes. Further research and development in this field are warranted to harness the full benefits of VR technology in CHD surgical management.


Asunto(s)
Cardiopatías Congénitas , Realidad Virtual , Humanos , Imagenología Tridimensional/métodos , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/cirugía , Corazón
2.
Int J Mol Sci ; 24(24)2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38139046

RESUMEN

Cognitive abilities tend to decline with aging, with variation between individuals, and many studies seek to identify genetic biomarkers that more accurately anticipate risks related to pathological aging. We investigated the influence of BDNF, NTRK2, and FNDC5 single nucleotide polymorphisms (SNPs) on the cognitive performance of young and older adults with contrasting educational backgrounds. We addressed three questions: (1) Is education associated with reduced age-related cognitive decline? (2) Does the presence of SNPs explain the variation in cognitive performance observed late in life? (3) Is education differentially associated with cognition based on the presence of BDNF, NTRK2, or FNDC5 polymorphisms? We measured the cognitive functions of young and older participants, with lower and higher education, using specific and sensitive tests of the Cambridge Automated Neuropsychological Test Assessment Battery. A three-way ANOVA revealed that SNPs were associated with differential performances in executive functions, episodic memory, sustained attention, mental and motor response speed, and visual recognition memory and that higher educational levels improved the affected cognitive functions. The results revealed that distinct SNPs affect cognition late in life differentially, suggesting their utility as potential biomarkers and emphasizing the importance of cognitive stimulation that advanced education early in life provides.


Asunto(s)
Disfunción Cognitiva , Memoria Episódica , Humanos , Anciano , Factor Neurotrófico Derivado del Encéfalo/genética , Disfunción Cognitiva/genética , Cognición/fisiología , Polimorfismo de Nucleótido Simple , Fibronectinas/genética , Biomarcadores , Pruebas Neuropsicológicas
3.
Molecules ; 28(14)2023 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-37513459

RESUMEN

Gastric cancer is one of the most frequent types of neoplasms worldwide, usually presenting as aggressive and difficult-to-manage tumors. The search for new structures with anticancer potential encompasses a vast research field in which natural products arise as promising alternatives. In this scenario, piperine, an alkaloid of the Piper species, has received attention due to its biological activity, including anticancer attributes. The present work proposes three heating-independent, reliable, low-cost, and selective methods for obtaining piperine from Piper nigrum L. (Black pepper). Electronic (SEM) and optical microscopies, X-ray diffraction, nuclear magnetic resonance spectroscopies (13C and 1H NMR), and optical spectroscopies (UV-Vis, photoluminescence, and FTIR) confirm the obtention of piperine crystals. The MTT assay reveals that the piperine samples exhibit good cytotoxic activity against primary and metastasis models of gastric cancer cell lines from the Brazilian Amazon. The samples showed selective cytotoxicity on the evaluated models, revealing higher effectiveness in cells bearing a higher degree of aggressiveness. Moreover, the investigated piperine crystals demonstrated the ability to act as a good cytotoxicity enhancer when combined with traditional chemotherapeutics (5-FU and GEM), allowing the drugs to achieve the same cytotoxic effect in cells employing lower concentrations. These results establish piperine as a promising molecule for therapy investigations in aggressive gastric cancer, both in its isolated form or as a bioenhancer.


Asunto(s)
Alcaloides , Antineoplásicos , Piper nigrum , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Alcaloides/química , Benzodioxoles/química , Piperidinas/química , Alcamidas Poliinsaturadas/química , Piper nigrum/química , Antineoplásicos/farmacología
4.
Curr Issues Mol Biol ; 44(5): 2275-2286, 2022 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-35678683

RESUMEN

Cancer is a multifactorial group of diseases, being highly incident and one of the leading causes of death worldwide. In Brazil, there is a great variation in cancer incidence and impact among the different geographic regions, partly due to the genetic heterogeneity of the population in this country, composed mainly by European (EUR), Native American (NAM), African (AFR), and Asian (ASN) ancestries. Among different populations, genetic markers commonly present diverse allelic frequencies, but in admixed populations, such as the Brazilian population, data is still limited, which is an issue that might influence cancer incidence. Therefore, we analyzed the allelic and genotypic distribution of 12 INDEL polymorphisms of interest in populations from the five Brazilian geographic regions and in populations representing EUR, NAM, AFR, and ASN, as well as tissue expression in silico. Genotypes were obtained by multiplex PCR and the statistical analyses were done using R, while data of tissue expression for each marker was extracted from GTEx portal. We highlight that all analyzed markers presented statistical differences in at least one of the population comparisons, and that we found 39 tissues to be differentially expressed depending on the genotype. Here, we point out the differences in genotype distribution and gene expression of potential biomarkers for risk of cancer development and we reinforce the importance of this type of study in populations with different genetic backgrounds.

5.
Curr Issues Mol Biol ; 44(2): 942-951, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-35723347

RESUMEN

piRNAs are a class of noncoding RNAs that perform functions in epigenetic regulation and silencing of transposable elements, a mechanism conserved among most mammals. At present, there are more than 30,000 known piRNAs in humans, of which more than 80% are derived from intergenic regions, and approximately 20% are derived from the introns and exons of pre-mRNAs. It was observed that the expression of the piRNA profile is specific in several organs, suggesting that they play functional roles in different tissues. In addition, some studies suggest that changes in regions that encode piRNAs may have an impact on their function. To evaluate the conservation of these regions and explore the existence of a seed region, SNP and INDEL variant rates were investigated in several genomic regions and compared to piRNA region variant rates. Thus, data analysis, data collection, cleaning, treatment, and exploration were implemented using the R programming language with the help of the RStudio platform. We found that piRNA regions are highly conserved after considering INDELs and do not seem to present an identifiable seed region after considering SNPs and INDEL variants. These findings may contribute to future studies attempting to determine how polymorphisms in piRNA regions can impact diseases.

6.
Curr Issues Mol Biol ; 44(11): 5498-5515, 2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36354684

RESUMEN

The WD repeat containing antisense to TP53 (WRAP53) gene codifies an antisense transcript for tumor protein p53 (TP53), stabilization (WRAP53α), and a functional protein (WRAP53ß, WDR79, or TCAB1). The WRAP53ß protein functions as a scaffolding protein that is important for telomerase localization, telomere assembly, Cajal body integrity, and DNA double-strand break repair. WRAP53ß is one of many proteins known for containing WD40 domains, which are responsible for mediating a variety of cell interactions. Currently, WRAP53 overexpression is considered a biomarker for a diverse subset of cancer types, and in this study, we describe what is known about WRAP53ß's multiple interactions in cell protein trafficking, Cajal body formation, and DNA double-strand break repair and its current perspectives as a biomarker for cancer.

7.
BMC Cancer ; 22(1): 1063, 2022 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-36243680

RESUMEN

BACKGROUND: Although penile cancer (PC) is uncommon in developed countries, it is widespread in developing countries. The state of Maranhão (Northeast, Brazil) has the highest global incidence recorded for PC, and, despite its socioeconomic vulnerability, it has been attributed to human papillomavirus (HPV) infection. This study aimed to determine the histopathological features, the prevalence of HPV infection, and the immunohistochemical profile of PC in Maranhão. METHODS: A retrospective cohort of 200 PC cases were evaluated. HPV detection was performed using nested-PCR followed by direct sequencing for genotyping. Immunohistochemistry (IHC) was performed using monoclonal antibodies anti-p16INK4a, p53, and ki-67. RESULTS: Our data revealed a delay of 17 months in diagnosis, a high rate of penile amputation (96.5%), and HPV infection (80.5%) in patients from Maranhão (Molecular detection). We demonstrated the high rate of HPV in PC also by histopathological and IHC analysis. Most patients presented koilocytosis (75.5%), which was associated with those reporting more than 10 different sexual partners during their lifetime (p = 0.001). IHC revealed frequent p16INK4a overexpression (26.0%) associated with basaloid (p < 0.001) and high-grade tumors (p = 0.008). Interestingly, p16 appears not to be a better prognostic factor in our disease-free survival analysis, as previously reported. We also demonstrated high ki-67 and p53 expression in a subset of cases, which was related to worse prognostic factors such as high-grade tumors, angiolymphatic and perineural invasion, and lymph node metastasis. We found a significant impact of high ki-67 (p = 0.002, log-rank) and p53 (p = 0.032, log-rank) expression on decreasing patients' survival, as well as grade, pT, stage, pattern, and depth of invasion (p < 0.05, log-rank). CONCLUSIONS: Our data reaffirmed the high incidence of HPV infection in PC cases from Maranhão and offer new insights into potential factors that may contribute to the high PC incidence in the region. We highlighted the possible association of HPV with worse clinical prognosis factors, differently from what was observed in other regions. Furthermore, our IHC analysis reinforces p16, ki-67, and p53 expression as important diagnosis and/or prognosis biomarkers, potentially used in the clinical setting in emerging countries such as Brazil.


Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Pene , Anticuerpos Monoclonales/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Humanos , Incidencia , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Papillomaviridae/metabolismo , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Neoplasias del Pene/epidemiología , Neoplasias del Pene/patología , Pronóstico , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/genética
8.
Int J Mol Sci ; 23(10)2022 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-35628297

RESUMEN

Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. Therefore, we sought to analyze studies that reported deregulated miRNA expression in HTLV-1 infected cells and patients' samples to understand how this deregulation could induce malignancy. Through in silico analysis, we identified 12 miRNAs that stood out in the prediction of targets, and we performed functional annotation of the genes linked to these 12 miRNAs that appeared to have a major biological interaction. A total of 90 genes were enriched in 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-ß, and Ras signaling pathways. These miRNAs and gene interactions are discussed in further detail for elucidation of how they may act as probable drivers for ATL onset, and while our data provide solid starting points for comprehension of miRNAs' roles in HTLV-1 infection, continuous effort in oncologic research is still needed to improve our understanding of HTLV-1 induced leukemia.


Asunto(s)
Infecciones por HTLV-I , Leucemia-Linfoma de Células T del Adulto , MicroARNs , Biología Computacional , Infecciones por HTLV-I/genética , Virus Linfotrópico T Tipo 1 Humano , Humanos , Leucemia-Linfoma de Células T del Adulto/genética , Leucemia-Linfoma de Células T del Adulto/virología , MicroARNs/genética
9.
Int J Mol Sci ; 23(15)2022 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-35897788

RESUMEN

The circadian clock (CC) is a daily system that regulates the oscillations of physiological processes and can respond to the external environment in order to maintain internal homeostasis. For the functioning of the CC, the clock genes (CG) act in different metabolic pathways through the clock-controlled genes (CCG), providing cellular regulation. The CC's interruption can result in the development of different diseases, such as neurodegenerative and metabolic disorders, as well as cancer. Leukemias correspond to a group of malignancies of the blood and bone marrow that occur when alterations in normal cellular regulatory processes cause the uncontrolled proliferation of hematopoietic stem cells. This review aimed to associate a deregulated CC with the manifestation of leukemia, looking for possible pathways involving CG and their possible role as leukemic biomarkers.


Asunto(s)
Trastornos Cronobiológicos , Relojes Circadianos , Leucemia , Neoplasias , Biomarcadores , Relojes Circadianos/genética , Ritmo Circadiano/genética , Humanos , Leucemia/genética
10.
Int J Mol Sci ; 23(7)2022 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-35409190

RESUMEN

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients' prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones' survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host's immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.


Asunto(s)
Neoplasias , Citotoxinas/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Factores Inmunológicos/uso terapéutico , Inmunoterapia/métodos , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Neoplasias/patología
11.
Pathobiology ; 88(2): 156-169, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33588422

RESUMEN

Identifying a microbiome pattern in gastric cancer (GC) is hugely debatable due to the variation resulting from the diversity of the studied populations, clinical scenarios, and metagenomic approach. H. pylori remains the main microorganism impacting gastric carcinogenesis and seems necessary for the initial steps of the process. Nevertheless, an additional non-H. pylori microbiome pattern is also described, mainly at the final steps of the carcinogenesis. Unfortunately, most of the presented results are not reproducible, and there are no consensual candidates to share the H. pylori protagonists. Limitations to reach a consistent interpretation of metagenomic data include contamination along every step of the process, which might cause relevant misinterpretations. In addition, the functional consequences of an altered microbiome might be addressed. Aiming to minimize methodological bias and limitations due to small sample size and the lack of standardization of bioinformatics assessment and interpretation, we carried out a comprehensive analysis of the publicly available metagenomic data from various conditions relevant to gastric carcinogenesis. Mainly, instead of just analyzing the results of each available publication, a new approach was launched, allowing the comprehensive analysis of the total sample amount, aiming to produce a reliable interpretation due to using a significant number of samples, from different origins, in a standard protocol. Among the main results, Helicobacter and Prevotella figured in the "top 6" genera of every group. Helicobacter was the first one in chronic gastritis (CG), gastric cancer (GC), and adjacent (ADJ) groups, while Prevotella was the leader among healthy control (HC) samples. Groups of bacteria are differently abundant in each clinical situation, and bacterial metabolic pathways also diverge along the carcinogenesis cascade. This information may support future microbiome interventions aiming to face the carcinogenesis process and/or reduce GC risk.


Asunto(s)
Microbioma Gastrointestinal/genética , Neoplasias Gástricas/microbiología , Biología Computacional , Mucosa Gástrica/microbiología , Microbioma Gastrointestinal/fisiología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Humanos , Redes y Vías Metabólicas , Metagenoma , Prevotella/genética , Prevotella/patogenicidad
12.
Mol Carcinog ; 59(6): 604-617, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32212199

RESUMEN

The incidence of penile cancer (PeCa) is increasing worldwide, however, the highest rates are reported in underdeveloped countries. The molecular mechanisms that underly the onset and progression of these tumors are still unclear. Therefore, our goal was to determine the genome-wide copy number alterations and the involvement of human papiloma virus (HPV) (TP53 and RB1), inflammatory (COX2 and EGFR), and PI3K/AKT pathway (AKT1, AKT2, EGFR, ERBB3, ERBB4, PIK3CA, and PTEN) associated genes in patients with PeCa from a high incidence region in Brazil (Maranhão). HPV genotyping was performed by nest-PCR and genome sequencing, copy number alterations (CNAs) by array comparative genomic hybridization and gene copy number status, gene, and protein expression by quantitative polymerase chain reaction, reverse transcriptase-quantitative polymerase chain reaction, and immunohistochemistry, respectively. HPV genotyping revealed one of the highest frequencies of HPV reported in PeCa, affecting 96.4% of the cases. The most common CNAs observed were located at the HPV integration sites, such as 2p12-p11.2 and 14q32.33, where ADAM 6, KIAA0125, LINC00226, LINC00221, and miR7641-2, are mapped. Increased copy number of ERBB3 and EGFR genes were observed in association with COX2 and EGFR overexpression, reinforcing the role of the inflammatory pathway in PeCa, and suggesting anti-EGFR and anti-COX2 inhibitors as promising therapies for PeCa. Additionally, TP53 and RB1 messenger RNA downregulation was observed, suggesting the occurrence of other mechanisms for repression of these oncoproteins, in addition to the canonical HPV/TP53/RB1 signaling pathway. Our data reinforce the role of epigenetic events in abnormal gene expression in HPV-associated carcinomas and suggest the pivotal role of HPV driving CNAs and controlling gene expression in PeCa.


Asunto(s)
Carcinoma de Células Escamosas/genética , Variaciones en el Número de Copia de ADN , Infecciones por Papillomavirus/complicaciones , Neoplasias del Pene/genética , ARN Mensajero/genética , Proteínas de Unión a Retinoblastoma/genética , Proteína p53 Supresora de Tumor/genética , Ubiquitina-Proteína Ligasas/genética , Adulto , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genómica , Humanos , Masculino , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Neoplasias del Pene/patología , Neoplasias del Pene/virología , Factores de Riesgo
13.
Eur J Clin Microbiol Infect Dis ; 38(9): 1591-1597, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31114971

RESUMEN

Despite being one of the most studied cancer-related infections, the relationship between Helicobacter pylori infection and gastric adenocarcinoma (GC) remains, in some points, obscure. Based on a critical analysis of the available literature regarding stomach microbiota, we aimed to shed light to a possible new interpretation of the current understanding about the Helicobacter pylori-related GC carcinogenesis. We analyzed data from the literature on Helicobacter pylori and other potential carcinogenic pathogens, in both benignant conditions and gastric adenocarcinoma. Helicobacter pylori is the dominant microorganism in benignant conditions as non-complicated gastritis. In atrophic gastritis, metaplasia and, mainly, in gastric adenocarcinoma, a strong reduction in Helicobacter pylori abundance, and increased occurrence of other microorganisms is strongly demonstrated by metagenomic experiments. While causing peptic disease and keeping the stomach's high acidity, Helicobacter pylori infection avoids gastric infection by carcinogenic intestinal microbiota. Nevertheless, Helicobacter pylori persistence may also provoke an atrophic gastritis, a condition that causes its own decline, due to a microenvironment modification, including reduced acidity, resulting in Helicobacter pylori substitution by a cancer-prone microbiota. This new interpretation might result in a dramatic modification on clinical management of Helicobacter pylori-related gastric disease.


Asunto(s)
Carcinogénesis , Disbiosis , Gastritis/microbiología , Microbioma Gastrointestinal , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Neoplasias Gástricas/microbiología , Gastritis Atrófica/microbiología , Humanos , Estómago/microbiología , Microambiente Tumoral
14.
BMC Cancer ; 18(1): 1055, 2018 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-30376837

RESUMEN

BACKGROUND: Several genetic and epigenetic alterations are related to the development and progression of Gastric Cancer (GC), one of those being the deregulated microRNA (miRNA) expression profile. miRNAs are small noncoding RNAs that negatively regulate the expression of thousands of genes, including oncogenes and tumor suppressor genes. Our group identified, in previous studies, some miRNAs that are differentially expressed in GC when compared to the gastric mucosa without cancer, including hsa-miR-29c and hsa-miR-135b. The aim of the study was to modulate the expression of the miRNAs hsa-miR-29c-5p and hsa-miR-135b-5p and evaluate the expression of their target genes in 2D and 3D cell cultures. METHODS: hsa-miR-29c-5p and hsa-miR-135b-5p expression profiles were modulated by transfecting mimics and antimiRs, respectively, in 2D and 3D cell cultures. The expression of the proteins coded by the genes CDC42, DNMT3A (target genes of hsa-miR-29c-5p) and APC (target gene of hsa-miR-135b-5p) were measured by Western Blot. RESULTS: Results showed that mimics and antimiRs transfection significantly altered the expression of both miRNAs, increasing the expression of hsa-miR-29c-5p and reducing the expression of hsa-miR-135b-5p, especially in the 3D culture of the cell lines. When analyzing the proteins expression, we observed that AGP01 and AGP03 cell lines transfected with mimics had a reduction in the levels of CDC42 and DNMT3A and all three cell lines transfected with antimiRs had an increase in the expression of the protein APC. CONCLUSION: We concluded that three-dimensional culture can be a more representative in vitro model that resembles better the in vivo reality. Our results also showed that hsa-miR-29c-5p is an important regulator of CDC42 and DNMT3A genes in the intestinal subtype gastric cancer and hsa-miR-135b-5p regulates the APC gene in both intestinal and diffuse subtypes of GC. Dysregulation in their expression, and consequently in their respectively signaling pathways, shows how these miRNAs can influence the carcinogenesis of different histological subtypes of gastric cancer.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Genes APC , MicroARNs/genética , Interferencia de ARN , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Línea Celular Tumoral , Biología Computacional/métodos , Perfilación de la Expresión Génica , Humanos , Modelos Biológicos , Clasificación del Tumor , Estadificación de Neoplasias , Transcriptoma
15.
Chin J Cancer Res ; 30(5): 564-567, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30510368

RESUMEN

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.

16.
Chin J Cancer Res ; 29(2): 137-143, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28536492

RESUMEN

Type 1 gastric neuroendocrine tumors (gNETs) are usually small lesions, restricted to mucosal and sub-mucosal layers of corpus and fundus, with low aggressive behavior, for the majority of cases. Nevertheless, some cases present aggressive behavior. The increasing incidence of gNETs brings together a new relevant problem: how to identify potentially aggressive type 1 gNETs. The challenging problem seems to be finding out signs or features able to predict potentially aggressive cases, allowing a tailored approach, since the involved societies dedicated to provide guidelines for management of these neoplasms apparently failed in producing staging systems able to accurately predict prognosis of these tumors. Additionally, it is also important to try to find out explanations for increasing incidence, as well as to identify potential targets aiming to reach better control of this neoplasia. Here, we discuss potential pathways implicated in aggressive behavior, as well as new strategies to improve clinical management of these tumors.

17.
Homeopathy ; 105(3): 265-269, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27473548

RESUMEN

BACKGROUND: CANOVA(®) (CA) is a homeopathic immunomodulator. It contains several homeopathic medicines prepares according to the Brazilian Pharmacopoeia. CA is indicated in clinical conditions in which the immune system is impaired and against tumors. N-methyl-N-nitrosourea (NMU) is an N-nitroso compound, with genotoxic/mutagenic properties. Although several studies have shown promising results in the use of CA, there are no studies reporting possible antigenotoxic effects. METHOD: This study evaluated the in vitro antigenotoxic and anticytotoxic effects of CA in human lymphocytes exposed to NMU. Samples of human lymphocytes that were subjected to different concentrations of a mixture containing CA and NMU were used. The genotoxicity/antigenotoxicity of CA was evaluated by the comet assay, anticytotoxicity was assessed by quantification of apoptosis and necrosis using acridine orange/ethidium bromide. RESULTS: CA significantly reduced DNA damage induced by NMU and reduced significantly the frequency of NMU-induced apoptosis after 24 h of treatment. CONCLUSION: CA has an important cytoprotective effect significantly reducing the DNA damage and apoptosis induced by the carcinogen NMU.


Asunto(s)
Venenos de Crotálidos/farmacología , Citoprotección , Daño del ADN/efectos de los fármacos , Homeopatía , Linfocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Adulto , Apoptosis , Células Cultivadas , Femenino , Humanos , Masculino , Metilnitrosourea/efectos adversos , Pruebas de Mutagenicidad
18.
BMC Gastroenterol ; 14: 179, 2014 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-25318991

RESUMEN

BACKGROUND: Helicobacter pylori (HP) and Epstein-Barr virus (EBV) have been associated with cancer development. We evaluated the prevalence of HP, HP CagA+ and EBV infection in gastric cancer (GC) samples from adults and in gastric tissues from patients who underwent upper endoscopy (UE). METHODS: Samples from UE and GC were collected to investigate the presence of HP infection and the HP virulence factor CagA by a urease test and PCR. The presence of EBV was detected by Eber-1 in situ hybridization. RESULTS: In UE, 85.5% of juvenile patients showed some degree of gastritis (45.3% of patients with mild gastritis and 54.7% with moderate/severe gastritis) and patients with mild gastritis were younger than patients with moderate/severe gastritis. Among adults, 48.7% presented mild gastritis and 51.3% moderate/severe gastritis. HP infection was detected in 0% of normal mucosa, 58.5% of juvenile gastritis patients, 69.2% of adult gastritis patients and 88% of GC patients. In these same groups, HP CagA+ was detected in 0%, 37.7%, 61.5% and 67.2% of tissue samples, respectively. In juvenile patients, HP infection was more common in those with gastritis than in normal samples (p = 0.004). The patients with either HP or HP CagA+ were older than patients without these pathogens (p < 0.05). In juvenile patients, HP infection was more frequent in cases of moderate/severe gastritis than in cases of mild gastritis (p = 0.026). Moreover, in patients with GC, HP infection was more frequent in males than in females (p = 0.023). GC patients with HP CagA+ were older than patients with HP CagA- (p = 0.027). HP CagA+ was more common in intestinal-type than diffuse-type GC (p = 0.012). HP CagA+ was also associated with lymph-node (p = 0.024) and distal (p = 0.005) metastasis. No association between EBV infection and HP infection or any clinicopathological variable was detected. CONCLUSIONS: Our results suggest that HP is involved in the pathophysiology of severe gastric lesions and in the development of GC, particularly when CagA+ is present. EBV was not the primary pathogenic factor in our samples.


Asunto(s)
Infecciones por Virus de Epstein-Barr/diagnóstico , Gastritis/diagnóstico , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori , Neoplasias Gástricas/microbiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antígenos Bacterianos/análisis , Proteínas Bacterianas/análisis , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/patología , Gastritis/patología , Gastroscopía , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Lactante , Persona de Mediana Edad , Estómago/química , Estómago/microbiología , Neoplasias Gástricas/patología , Neoplasias Gástricas/virología , Adulto Joven
19.
PLoS One ; 19(4): e0299993, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38568963

RESUMEN

The selection of proper reference genes is critical for accurate gene expression analysis in all fields of biological and medical research, mainly because there are many distinctions between different tissues and specimens. Given this variability, even in known classic reference genes, demands of a comprehensive analysis platform is needed to identify the most suitable genes for each study. For this purpose, we present an analysis tool for assisting in decision-making in the analysis of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) data. EndoGeneAnalyzer, an open-source web tool for reference gene analysis in RT-qPCR studies, was used to compare the groups/conditions under investigation. This interactive application offers an easy-to-use interface that allows efficient exploration of datasets. Through statistical and stability analyses, EndoGeneAnalyzer assists in the select of the most appropriate reference gene or set of genes for each condition. It also allows researchers to identify and remove unwanted outliers. Moreover, EndoGeneAnalyzer provides a graphical interface to compare the evaluated groups, providing a visually informative differential analysis.


Asunto(s)
Perfilación de la Expresión Génica , Reacción en Cadena en Tiempo Real de la Polimerasa , Estándares de Referencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
20.
Nat Prod Res ; 38(10): 1806-1811, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37300460

RESUMEN

Acmella oleracea (L.) is a plant popularly known as jambu in the Brazilian Amazon. This species has several biological properties, such as anaesthetic, antioxidant and anti-inflammatory activities, among others. However, there is limited information on its anticancer activity. In this context, this study aims to evaluate the effects of the hydroethanolic extract of jambu and its active compound (spilanthol) on gastric cancer cells. Hydroethanolic jambu inflorescence extract was obtained, and spilanthol was isolated by HPLC. Biological cytotoxicity assays were determined using MTT tests. In addition, an in silico study using molecular docking evaluated the inhibitory properties of spilanthol against JAK1 and JAK2 proteins. The results showed that the hydroethanolic extract and the isolated compound spilanthol exhibited cytotoxicity against cancer cells. Molecular docking revealed that spilanthol has inhibitory potential for JAK1 and JAK2 proteins. Thus, extract of jambu and spilanthol can be a possible candidate for the treatment of gastric carcinoma.


Asunto(s)
Asteraceae , Neoplasias Gástricas , Humanos , Simulación del Acoplamiento Molecular , Alcamidas Poliinsaturadas , Extractos Vegetales/farmacología
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