Publications by authors named "Cristian Arriaga-Canon"

13 Publications

  • Page 1 of 1

Indolaminergic System in Adult Rat Testes: Evidence for a Local Serotonin System.

Front Neuroanat 2020 19;14:570058. Epub 2021 Feb 19.

Instituto Nacional de Pediatría, Ciudad de México, Mexico.

Serotonin (5-HT) is member of a family of indolamine molecules that participate in a wide variety of biological processes. Despite its important role in the regulation of local blood systems, little is known about the physiological function of 5-HT in reproductive organs, its functional implications, and its role in the reproduction of mammals. In the present work, we evaluated the localization and distribution of 5-HT (using histochemical analysis of indolamines) and different components of the serotoninergic system in rat testes. We detected local synthesis and degradation through immunofluorescence and western blot analyses against the TPH1, MAO, 5-HT, and VMAT1 serotonin transporters. We also identified the localization and distribution of the 5-HT, 5-HT, and 5-HT receptors. RT-PCR results showed the presence of the Tph1, Maoa, Slc6a4, and Htr3a genes in testes and in the brain stem (Tph1 was used as a negative control). High-performance liquid chromatography was used to determine the presence of 5-HT and the activity of tryptophan hydroxylase in testes homogenates . Our observations suggest that TPH1 activity and local 5-HT synthesis befall in rat testes. We propose that 5-HT could participate in the regulation of testosterone synthesis and in the spermatogenesis process via local serotoninergic system. However, more studies are needed before concluding that rat testes, or those of other mammals, contain an active form of tryptophan hydroxylase and produce 5-HT.
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http://dx.doi.org/10.3389/fnana.2020.570058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933592PMC
February 2021

Saliva is a reliable and accessible source for the detection of SARS-CoV-2.

Int J Infect Dis 2021 Apr 11;105:83-90. Epub 2021 Feb 11.

Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico.

Objectives: The aim of this study was to investigate the feasibility of saliva sampling as a non-invasive and safer tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to compare its reproducibility and sensitivity with nasopharyngeal swab samples (NPS). The use of sample pools was also investigated.

Methods: A total of 2107 paired samples were collected from asymptomatic healthcare and office workers in Mexico City. Sixty of these samples were also analyzed in two other independent laboratories for concordance analysis. Sample processing and analysis of virus genetic material were performed according to standard protocols described elsewhere. A pooling analysis was performed by analyzing the saliva pool and the individual pool components.

Results: The concordance between NPS and saliva results was 95.2% (kappa 0.727, p = 0.0001) and 97.9% without considering inconclusive results (kappa 0.852, p = 0.0001). Saliva had a lower number of inconclusive results than NPS (0.9% vs 1.9%). Furthermore, saliva showed a significantly higher concentration of both total RNA and viral copies than NPS. Comparison of our results with those of the other two laboratories showed 100% and 97% concordance. Saliva samples are stable without the use of any preservative, and a positive SARS-CoV-2 sample can be detected 5, 10, and 15 days after collection when the sample is stored at 4 °C.

Conclusions: The study results indicate that saliva is as effective as NPS for the identification of SARS-CoV-2-infected asymptomatic patients. Sample pooling facilitates the analysis of a larger number of samples, with the benefit of cost reduction.
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http://dx.doi.org/10.1016/j.ijid.2021.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876483PMC
April 2021

Epidrug Repurposing: Discovering New Faces of Old Acquaintances in Cancer Therapy.

Front Oncol 2020 18;10:605386. Epub 2020 Nov 18.

Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico.

Gene mutations are strongly associated with tumor progression and are well known in cancer development. However, recently discovered epigenetic alterations have shown the potential to greatly influence tumoral response to therapy regimens. Such epigenetic alterations have proven to be dynamic, and thus could be restored. Due to their reversible nature, the promising opportunity to improve chemotherapy response using epigenetic therapy has arisen. Beyond helping to understand the biology of the disease, the use of modern clinical epigenetics is being incorporated into the management of the cancer patient. Potential epidrug candidates can be found through a process known as drug repositioning or repurposing, a promising strategy for the discovery of novel potential targets in already approved drugs. At present, novel epidrug candidates have been identified in preclinical studies and some others are currently being tested in clinical trials, ready to be repositioned. This epidrug repurposing could circumvent the classic paradigm where the main focus is the development of agents with one indication only, while giving patients lower cost therapies and a novel precision medical approach to optimize treatment efficacy and reduce toxicity. This review focuses on the main approved epidrugs, and their druggable targets, that are currently being used in cancer therapy. Also, we highlight the importance of epidrug repurposing by the rediscovery of known chemical entities that may enhance epigenetic therapy in cancer, contributing to the development of precision medicine in oncology.
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http://dx.doi.org/10.3389/fonc.2020.605386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708379PMC
November 2020

Prognostic Significance of the MAD1L1 1673 G: A Polymorphism in Ovarian Adenocarcinomas.

Rev Invest Clin 2020 12 22;72(6):372-379. Epub 2020 Dec 22.

Cancer Biomedical Research Unit, Instituto Nacional de Cancerología, SSA-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM); Instituto Nacional de Medicina Genómica; Mexico City, Mexico.

Background: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy.

Objective: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma.

Methods: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics.

Results: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele.

Conclusions: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism.
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http://dx.doi.org/10.24875/RIC.19003280DOI Listing
December 2020

Prognostic Significance of the MAD1L1 1673 G: A Polymorphism in Ovarian Adenocarcinomas.

Rev Invest Clin 2020 May 7;73(3). Epub 2020 May 7.

Cancer Biomedical Research Unit, Instituto Nacional de Cancerología, SSA-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM); Instituto Nacional de Medicina Genómica; Mexico City, Mexico.

Background: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy.

Objective: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma.

Methods: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics.

Results: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele.

Conclusions: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism.
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May 2020

The Promising Role of miR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics.

Mol Ther Nucleic Acids 2020 Jun 13;20:409-420. Epub 2020 Mar 13.

Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Avenida San Fernando No. 22, Colonia Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico; Instituto Nacional de Medicina Genómica, Periferico Sur 4809, Arenal Tepepan, Tlalpan, CP 14610, Mexico City, Mexico. Electronic address:

MicroRNAs are small noncoding transcripts that posttranscriptionally regulate gene expression via base-pairing complementarity. Their role in cancer can be related to tumor suppression or oncogenic function. Moreover, they have been linked to processes recognized as hallmarks of cancer, such as apoptosis, invasion, metastasis, and proliferation. Particularly, one of the first oncomiRs found upregulated in a variety of cancers, such as gliomas, breast cancer, and colorectal cancer, was microRNA-21 (miR-21). Some of its target genes associated with cancer are PTEN (phosphatase and tensin homolog), PDCD4 (programmed cell death protein 4), RECK (reversion-inducing cysteine-rich protein with Kazal motifs), and STAT3 (signal transducer activator of transcription 3). As a result, miR-21 has been proposed as a plausible diagnostic and prognostic biomarker, as well as a therapeutic target for several types of cancer. Currently, research and clinical trials to inhibit miR-21 through anti-miR-21 oligonucleotides and ADM-21 are being conducted. As all of the evidence suggests, miR-21 is involved in carcinogenic processes; therefore, inhibiting it could have effects on more than one type of cancer. However, whether miR-21 can be used as a tissue-specific biomarker should be analyzed with caution. Consequently, the purpose of this review is to outline the available information and recent advances regarding miR-21 as a potential biomarker in the clinical setting and as a therapeutic target in cancer to highlight its importance in the era of precision medicine.
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http://dx.doi.org/10.1016/j.omtn.2020.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118281PMC
June 2020

MicroRNAs in Tumor Cell Metabolism: Roles and Therapeutic Opportunities.

Front Oncol 2019 11;9:1404. Epub 2019 Dec 11.

Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología - Instituto de Investigaciones Biomédicas - Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.

Dysregulated metabolism is a common feature of cancer cells and is considered a hallmark of cancer. Altered tumor-metabolism confers an adaptive advantage to cancer cells to fulfill the high energetic requirements for the maintenance of high proliferation rates, similarly, reprogramming metabolism confers the ability to grow at low oxygen concentrations and to use alternative carbon sources. These phenomena result from the dysregulated expression of diverse genes, including those encoding microRNAs (miRNAs) which are involved in several metabolic and tumorigenic pathways through its post-transcriptional-regulatory activity. Further, the identification of key actionable altered miRNA has allowed to propose novel targeted therapies to modulated tumor-metabolism. In this review, we discussed the different roles of miRNAs in cancer cell metabolism and novel miRNA-based strategies designed to target the metabolic machinery in human cancer.
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http://dx.doi.org/10.3389/fonc.2019.01404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917641PMC
December 2019

Mexican BRCA1 founder mutation: Shortening the gap in genetic assessment for hereditary breast and ovarian cancer patients.

PLoS One 2019 23;14(9):e0222709. Epub 2019 Sep 23.

Hereditary Cancer Clinic, National Cancer Institute, Mexico city, Mexico.

The deletion of exons 9 to 12 of BRCA1 (9-12 del BRCA1) is considered a founder mutation in the Mexican population. We evaluate the usefulness of the target detection of 9-12 del BRCA1 as the first molecular diagnostic strategy in patients with Hereditary Breast and Ovarian Cancer (HBOC). We performed the genetic assessment of 637 patients with suspected HBOC. The region corresponding to the breakpoints for the 9-12 del BRCA1 was amplified by polymerase chain reaction (PCR). An analysis of the clinical data of the carriers and non-carriers was done, searching for characteristics that correlated with the deletion. The 9-12 del BRCA1 was detected in 5% of patients with suspected HBOC (30/637). In patients diagnosed with ovarian cancer, 13 of 30 were 9-12 del BRCA1 carriers, which represents 43%. We found a significant association between the 9-12 del BRCA1 carriers with triple negative breast cancer and high-grade papillary serous ovarian cancer. We concluded that the detection of the 9-12 del BRCA1 is useful as a first molecular diagnostic strategy in the Mexican population. In particular, it shortens the gap in genetic assessment in patients with triple negative breast cancer and ovarian cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222709PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756553PMC
March 2020

[Clinical Applications of Next-Generation Sequencing].

Rev Invest Clin 2018 ;70(4):153-157

Genomics Laboratory, Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México - Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

The significant drop in sequencing costs boosted by chemistries optimization and sample multiplexation has resulted in an immense growth within the field of next-generation sequencing (NGS) in the last decade. This has allowed a diversification of techniques, promoting a rapid advance in knowledge on the molecular basis of human disease. Due to the applicability and importance of this technology in basic research, it has quickly migrated to the clinical setting. NGS enables clinicians to make improved diagnostic and treatment decisions, which ultimately may influence precision medicine.
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http://dx.doi.org/10.24875/RIC.18002544DOI Listing
December 2018

The use of long non-coding RNAs as prognostic biomarkers and therapeutic targets in prostate cancer.

Oncotarget 2018 Apr 17;9(29):20872-20890. Epub 2018 Apr 17.

Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Tlalpan. C.P. 14080, CDMX, Mexico.

Prostate cancer is the most common cancer in men and the second leading cause of cancer-related deaths. The most used biomarker to detect prostate cancer is Prostate Specific Antigen (PSA), whose levels are measured in serum. However, it has been recently established that molecular markers of cancer should not be based solely on genes and proteins but should also reflect other genomic traits; long non-coding RNAs (lncRNAs) serve this purpose. lncRNAs are transcripts of >200 bases that do not encode proteins and that have been shown to display abnormal expression profiles in different types of cancer. Experimental studies have highlighted lncRNAs as potential biomarkers for prognoses and treatments in patients with different types of cancer, including prostate cancer, where the PCA3 lncRNA is currently used as a diagnostic tool and management strategy. With the development of genomic technologies, particularly next-generation sequencing (NGS), several other lncRNAs have been linked to prostate cancer and are currently under validation for their medical use. In this review, we will discuss different strategies for the discovery of novel lncRNAs that can be evaluated as prognostic biomarkers, the clinical impact of these lncRNAs and how lncRNAs can be used as potential therapeutic targets.
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http://dx.doi.org/10.18632/oncotarget.25038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945524PMC
April 2018

Molecular features of influenza A (H1N1)pdm09 prevalent in Mexico during winter seasons 2012-2014.

PLoS One 2017 10;12(7):e0180419. Epub 2017 Jul 10.

Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.

Since the emergence of the pandemic H1N1pdm09 virus in Mexico and California, biannual increases in the number of cases have been detected in Mexico. As observed in previous seasons, pandemic A/H1N1 09 virus was detected in severe cases during the 2011-2012 winter season and finally, during the 2013-2014 winter season it became the most prevalent influenza virus. Molecular and phylogenetic analyses of the whole viral genome are necessary to determine the antigenic and pathogenic characteristics of influenza viruses that cause severe outcomes of the disease. In this paper, we analyzed the evolution, antigenic and genetic drift of Mexican isolates from 2009, at the beginning of the pandemic, to 2014. We found a clear variation of the virus in Mexico from the 2011-2014 season due to different markers and in accordance with previous reports. In this study, we identified 13 novel substitutions with important biological effects, including virulence, T cell epitope presented by MHC and host specificity shift and some others substitutions might have more than one biological function. The systematic monitoring of mutations on whole genome of influenza A pH1N1 (2009) virus circulating at INER in Mexico City might provide valuable information to predict the emergence of new pathogenic influenza virus.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180419PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503254PMC
September 2017

A long non-coding RNA promotes full activation of adult gene expression in the chicken α-globin domain.

Epigenetics 2014 Jan 6;9(1):173-81. Epub 2013 Nov 6.

Instituto de Fisiología Celular; Departamento de Genética Molecular; Universidad Nacional Autónoma de México; Distrito Federal, México.

Long non-coding RNAs (lncRNAs) were recently shown to regulate chromatin remodelling activities. Their function in regulating gene expression switching during specific developmental stages is poorly understood. Here we describe a nuclear, non-coding transcript responsive for the stage-specific activation of the chicken adult α(D) globin gene. This non-coding transcript, named α-globin transcript long non-coding RNA (lncRNA-αGT) is transcriptionally upregulated in late stages of chicken development, when active chromatin marks the adult α(D) gene promoter. Accordingly, the lncRNA-αGT promoter drives erythroid-specific transcription. Furthermore, loss of function experiments showed that lncRNA-αGT is required for full activation of the α(D) adult gene and maintenance of transcriptionally active chromatin. These findings uncovered lncRNA-αGT as an important part of the switching from embryonic to adult α-globin gene expression, and suggest a function of lncRNA-αGT in contributing to the maintenance of adult α-globin gene expression by promoting an active chromatin structure.
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http://dx.doi.org/10.4161/epi.27030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928180PMC
January 2014

CTCF demarcates chicken embryonic α-globin gene autonomous silencing and contributes to adult stage-specific gene expression.

Epigenetics 2013 Aug 3;8(8):827-38. Epub 2013 Jul 3.

Instituto de Fisiología Celular; Departamento de Genética Molecular; Universidad Nacional Autónoma de México; México D.F., México.

Genomic loci composed of more than one gene are frequently subjected to differential gene expression, with the chicken α-globin domain being a clear example. In the present study we aim to understand the globin switching mechanisms responsible for the epigenetic silencing of the embryonic π gene and the transcriptional activation of the adult α(D) and α(A) genes at the genomic domain level. In early stages, we describe a physical contact between the embryonic π gene and the distal 3' enhancer that is lost later during development. We show that such a level of regulation is achieved through the establishment of a DNA hypermethylation sub-domain that includes the embryonic gene and the adjacent genomic sequences. The multifunctional CCCTCC-binding factor (CTCF), which is located upstream of the α(D) gene promoter, delimits this sub-domain and creates a transition between the inactive sub-domain and the active sub-domain, which includes the adult α(D) gene. In avian-transformed erythroblast HD3 cells that are induced to differentiate, we found active DNA demethylation of the adult α(D) promoter, coincident with the incorporation of 5-hydroxymethylcytosine (5hmC) and concomitant with adult gene transcriptional activation. These results suggest that autonomous silencing of the embryonic π gene is needed to facilitate an optimal topological conformation of the domain. This model proposes that CTCF is contributing to a specific chromatin configuration that is necessary for differential α-globin gene expression during development.
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http://dx.doi.org/10.4161/epi.25472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883786PMC
August 2013