Publications by authors named "Rocío Ortíz López"

101 Publications

Serological Test to Determine Exposure to SARS-CoV-2: ELISA Based on the Receptor-Binding Domain of the Spike Protein (S-RBD) Expressed in .

Diagnostics (Basel) 2021 Feb 10;11(2). Epub 2021 Feb 10.

Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, Monterrey CP 64849, NL, Mexico.

Massive worldwide serological testing for SARS-CoV-2 is needed to determine the extent of virus exposure in a particular region, the ratio of symptomatic to asymptomatic infected persons, and the duration and extent of immunity after infection. To achieve this, the development and production of reliable and cost-effective SARS-CoV-2 antigens is critical. We report the bacterial production of the peptide S-RBD, which contains the receptor-binding domain of the SARS-CoV-2 spike protein (region of 193 amino acid residues from asparagine-318 to valine-510) of the SARS-CoV-2 spike protein. We purified this peptide using a straightforward approach involving bacterial lysis, his-tag-mediated affinity chromatography, and imidazole-assisted refolding. The antigen performances of S-RBD and a commercial full-length spike protein were compared in ELISAs. In direct ELISAs, where the antigen was directly bound to the ELISA surface, both antigens discriminated sera from non-exposed and exposed individuals. However, the discriminating resolution was better in ELISAs that used the full-spike antigen than the S-RBD. Attachment of the antigens to the ELISA surface using a layer of anti-histidine antibodies gave equivalent resolution for both S-RBD and the full-length spike protein. Results demonstrate that ELISA-functional SARS-CoV-2 antigens can be produced in bacterial cultures, and that S-RBD may represent a cost-effective alternative to the use of structurally more complex antigens in serological COVID-19 testing.
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http://dx.doi.org/10.3390/diagnostics11020271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916330PMC
February 2021

miRNA signature associated with R-CHOP refractoriness in patients diagnosed with diffuse large B cell lymphoma.

Noncoding RNA Res 2020 Dec 10;5(4):185-190. Epub 2020 Oct 10.

Universidad Autonoma de Nuevo Leon, Facultad de Medicina, Mexico.

Refractoriness remains as one of the challenges in patients with lymphoma under chemotherapy, and among biological regulators in cells driving this type of response are microRNAs (miRNAs). Different genes are constantly turned on or off according to the miRNAs expression profiles affecting the drug response in patients and their stability in serum and plasma makes them potential prognostic biomarkers in several diseases. Here we described a profile of miRNAs in plasma of diffuse large B cell lymphoma (DLBCL) patients. miRNA expression arrays were carried using pre-treatment plasma samples of sixteen patients, followed by a comparison between the responder and the non-responders. After six cycles of R-CHOP treatment, twelve out of sixteen patients were clinically diagnosed with complete response while in four patients no clinical response was observed. Between these groups, a signature of fifteen differential expressed miRNAs was found. The circulating miRNAs in plasma of patients with no response were related to the drug resistance in other types of cancer, by targeting genes involved in cell proliferation and apoptosis, among other cell processes.
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http://dx.doi.org/10.1016/j.ncrna.2020.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585044PMC
December 2020

Immunotyping of tumor-infiltrating lymphocytes in triple-negative breast cancer and genetic characterization.

Oncol Lett 2020 Nov 20;20(5):140. Epub 2020 Aug 20.

Breast Cancer Center, Hospital San José, TecSalud, Tecnológico de Monterrey, Monterrey, Nuevo León 64710, México.

Tumor-infiltrating lymphocytes (TILs) reflect the host immune response against cancer cells. Immunomodulators have been recently suggested as a novel therapeutic strategy against triple-negative breast cancer (TNBC). However, the TIL profile in TNBC has not been thoroughly investigated. In the present study, the percentage, immunophenotype and genetic profiles of TILs in pre-surgical tumor samples of patients with TNBC were evaluated prior to neoadjuvant chemotherapy (NAC). Patients diagnosed with breast cancer at Hospital San José TecSalud were consecutively and prospectively enrolled in the present study between August 2011 and August 2015. The pathological response to NAC was evaluated using the de Miller-Payne and MD Anderson Cancer Center system. TIL percentage (low, intermediate, and high) was evaluated using special hematoxylin-eosin staining on the core needle biopsies. The immunophenotype of TILs was assessed by immunohistochemistry (IHC) for CD3, CD4 and CD8. In addition, the gene expression profile of , forkhead box P3, interleukin 6, programmed cell death 1 and CD274 molecule was assessed in all patients. A total of 26 samples from patients with TNBC prior to NAC were included in the present study. TILs were low in 30.7%, intermediate in 38.4% and elevated in 30.7% of tumors. CD3 and CD4 counts were associated with the pathological response to NAC (P=0.04). Finally, an overexpression pattern of and genes was observed in patients with a partial or complete pathological response. The present results demonstrated that TILs may predict the pathological response to NAC in patients with TNBC. Furthermore, a more accurate association was identified between the high expression levels of and genes and partial and complete pathological response, compared with the association between high expression and IHC alone.
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http://dx.doi.org/10.3892/ol.2020.12000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471657PMC
November 2020

Sequencing technology status of 2 testing in Latin American Countries.

NPJ Genom Med 2020 2;5:22. Epub 2020 Jun 2.

Department of Cancer Biology and Genetics, Division of Human Genetics, Department of Internal Medicine, Comprehensive Cancer Center, the Ohio State University, Columbus, OH United States.

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http://dx.doi.org/10.1038/s41525-020-0126-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265546PMC
June 2020

Everolimus for cardiac rhabdomyomas in children with tuberous sclerosis. The ORACLE study protocol (everOlimus for caRdiac rhAbdomyomas in tuberous sCLErosis): a randomised, multicentre, placebo-controlled, double-blind phase II trial.

Cardiol Young 2020 Mar 27;30(3):337-345. Epub 2020 Jan 27.

Pediatric Cardiology Department, Dr Alzir Bernardino Alves Pediatric Hospital and Maternity, Vila Velha, Espírito Santo, Brazil.

Introduction: Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.

Methods: ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.

Conclusions: ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
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http://dx.doi.org/10.1017/S1047951119003147DOI Listing
March 2020

Genetic variants in CYP2A6 and UGT1A9 genes associated with urinary nicotine metabolites in young Mexican smokers.

Pharmacogenomics J 2020 08 21;20(4):586-594. Epub 2020 Jan 21.

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico.

Nicotine is the major pharmacologically active substance in tobacco. Several studies have examined genotypes related to nicotine metabolism, but few studies have been performed in the Mexican population. The objective was to identify associations between gene variants in metabolizing enzymes and the urinary levels of nicotine metabolites among Mexican smokers. The levels of nicotine and its metabolites were determined in the urine of 88 young smokers from Mexico, and 167 variants in 24 genes associated with nicotine metabolism were genotyped by next-generation sequencing (NGS). Trans-3'-hydroxy-cotinine (3HC) and 4-hydroxy-4-(3-pyridyl)-butanoic acid were the most abundant metabolites (35 and 17%, respectively). CYP2A6*12 was associated with 3HC (p = 0.014). The rs145014075 was associated with creatinine-adjusted levels of nicotine (p = 0.035), while the rs12471326 (UGT1A9) was associated to cotinine-N-glucuronide (p = 0.030). CYP2A6 and UGT1A9 variants are associated to nicotine metabolism. 4HPBA metabolite was an abundant urinary metabolite in young Mexican smokers.
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http://dx.doi.org/10.1038/s41397-020-0147-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375952PMC
August 2020

Landscape of Germline Mutations in DNA Repair Genes for Breast Cancer in Latin America: Opportunities for PARP-Like Inhibitors and Immunotherapy.

Genes (Basel) 2019 10 10;10(10). Epub 2019 Oct 10.

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64710, Mexico.

Germline mutations in and () genes are present in about 50% of cases of hereditary breast cancer. Proteins encoded by these genes are key players in DNA repair by homologous recombination (HR). Advances in next generation sequencing and gene panels for breast cancer testing have generated a large amount of data on gene variants implicated in hereditary breast cancer, particularly in genes such as , , , , , and . These genes are involved in DNA repair. Most of these variants have been reported for Caucasian, Jewish, and Asian population, with few reports for other communities, like those in Latin American (LA) countries. We reviewed 81 studies from 11 LA countries published between 2000 and 2019 but most of these studies focused on genes. In addition to these genes, breast cancer-related variants have been reported for , , , , , , , , and genes. Some of these variants are unique to LA populations. This analysis may contribute to enhance breast cancer variant characterization, and thus to find therapies and implement precision medicine for LA communities.
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http://dx.doi.org/10.3390/genes10100786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827033PMC
October 2019

The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors.

Materials (Basel) 2019 Sep 11;12(18). Epub 2019 Sep 11.

Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, Monterrey, Nuevo León CP 64849, Mexico.

The ideal in vitro recreation of the micro-tumor niche-although much needed for a better understanding of cancer etiology and development of better anticancer therapies-is highly challenging. Tumors are complex three-dimensional (3D) tissues that establish a dynamic cross-talk with the surrounding tissues through complex chemical signaling. An extensive body of experimental evidence has established that 3D culture systems more closely recapitulate the architecture and the physiology of human solid tumors when compared with traditional 2D systems. Moreover, conventional 3D culture systems fail to recreate the dynamics of the tumor niche. Tumor-on-chip systems, which are microfluidic devices that aim to recreate relevant features of the tumor physiology, have recently emerged as powerful tools in cancer research. In tumor-on-chip systems, the use of microfluidics adds another dimension of physiological mimicry by allowing a continuous feed of nutrients (and pharmaceutical compounds). Here, we discuss recently published literature related to the culture of solid tumor-like tissues in microfluidic systems (tumor-on-chip devices). Our aim is to provide the readers with an overview of the state of the art on this particular theme and to illustrate the toolbox available today for engineering tumor-like structures (and their environments) in microfluidic devices. The suitability of tumor-on-chip devices is increasing in many areas of cancer research, including the study of the physiology of solid tumors, the screening of novel anticancer pharmaceutical compounds before resourcing to animal models, and the development of personalized treatments. In the years to come, additive manufacturing (3D bioprinting and 3D printing), computational fluid dynamics, and medium- to high-throughput omics will become powerful enablers of a new wave of more sophisticated and effective tumor-on-chip devices.
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http://dx.doi.org/10.3390/ma12182945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766252PMC
September 2019

Polymorphisms -455G/A and -148C/T and Fibrinogen Plasmatic Level as Risk Markers of Coronary Disease and Major Adverse Cardiovascular Events.

Dis Markers 2019 1;2019:5769514. Epub 2019 Jul 1.

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico.

Some polymorphisms in genes codifying for fibrinogen have been correlated with plasma levels of this protein, and several studies reported their associations with acute cardiovascular events. In the present study, 118 subjects with unstable and stable coronary diseases were enrolled to determinate the associations among fibrinogen gene polymorphisms, plasma fibrinogen levels, and major cardiovascular adverse events in a sample of southwestern Mexico. The groups, including 81 control subjects, were matched for age, sex, body mass index, and sedentarism. Plasma fibrinogen levels and the polymorphisms 455G/A, -148C/T, +1689T/G, and I of the gene of fibrinogen were compared in all groups. Plasma fibrinogen levels (>465 mg/dl) were significant in patients with coronary disease. Fibrinogen plasma values > 450 mg/dl were associated with cardiovascular mortality during the follow-up analysis of the unstable coronary disease group ( = 0.04). The allelic loads of -455A and -148T were associated with plasma fibrinogen levels > 450 mg/dl ( < 0.003 and = 0.03, respectively) and with coronary disease ( = 0.016 and < 0.006, respectively). The follow-up of posterior events after an acute coronary event showed that the genetic load of the -148T allele was associated with major adverse cardiovascular events (RR = 1.8, 95%CI = 1.01-3.35, = 0.04). Fibrinogen plasmatic levels > 450 mg/dl and the fibrinogen polymorphisms -455G/A and 148C/T had association with MACE and coronary disease. This study suggests that these gene polymorphisms are associated with cardiovascular risk.
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http://dx.doi.org/10.1155/2019/5769514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636499PMC
December 2019

Spatial Clusters of Children with Cleft Lip and Palate and Their Association with Polluted Zones in the Monterrey Metropolitan Area.

Int J Environ Res Public Health 2019 07 12;16(14). Epub 2019 Jul 12.

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud. Monterrey 64710, Mexico.

This study examines the spatial structure of children with cleft lip and palate (CLP) and its association with polluted areas in the Monterrey Metropolitan Area (MMA). The Nearest Neighbor Index (NNI) and the Spatial Statistical Scan (SaTScan) determined that the CLP cases are agglomerated in spatial clusters distributed in different areas of the city, some of them grouping up to 12 cases of CLP in a radius of 1.2 km. The application of the interpolation by empirical Bayesian kriging (EBK) and the inverse distance weighted (IDW) method showed that 95% of the cases have a spatial interaction with values of particulate matter (PM) of more than 50 points. The study also shows that 83% of the cases interacted with around 2000 annual tons of greenhouse gases. This study may contribute to other investigations applying techniques for the identification of environmental and genetic factors possibly associated with congenital malformations and for determining the influence of contaminating substances in the incidence of these diseases, particularly CLP.
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http://dx.doi.org/10.3390/ijerph16142488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678111PMC
July 2019

A Bioactive Cartilage Graft of IGF1-Transduced Adipose Mesenchymal Stem Cells Embedded in an Alginate/Bovine Cartilage Matrix Tridimensional Scaffold.

Stem Cells Int 2019 18;2019:9792369. Epub 2019 Apr 18.

Universidad Autónoma de Nuevo León (UANL), Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Monterrey, NL, Mexico.

Articular cartilage injuries remain as a therapeutic challenge due to the limited regeneration potential of this tissue. Cartilage engineering grafts combining chondrogenic cells, scaffold materials, and microenvironmental factors are emerging as promissory alternatives. The design of an adequate scaffold resembling the physicochemical features of natural cartilage and able to support chondrogenesis in the implants is a crucial topic to solve. This study reports the development of an implant constructed with IGF1-transduced adipose-derived mesenchymal stem cells (immunophenotypes: CD105, CD90, CD73, CD14, and CD34) embedded in a scaffold composed of a mix of alginate/milled bovine decellularized knee material which was cultivated for 28 days (3CI). Histological analyses demonstrated the distribution into isogenous groups of chondrocytes surrounded by a de novo dense extracellular matrix with balanced proportions of collagens II and I and high amounts of sulfated proteoglycans which also evidenced adequate cell proliferation and differentiation. This graft also shoved mechanical properties resembling the natural knee cartilage. A modified Bern/O'Driscoll scale showed that the 3CI implants had a significantly higher score than the 2CI implants lacking cells transduced with IGF1 (16/18 vs. 14/18), representing high-quality engineering cartilage suitable for tests. This study suggests that this graft resembles several features of typical hyaline cartilage and will be promissory for preclinical studies for cartilage regeneration.
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http://dx.doi.org/10.1155/2019/9792369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501174PMC
April 2019

Genetic alterations of triple negative breast cancer (TNBC) in women from Northeastern Mexico.

Oncol Lett 2019 Mar 29;17(3):3581-3588. Epub 2019 Jan 29.

Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Monterrey, Nuevo Leon 64710, Mexico.

Triple negative breast cancer (TNBC) is a subtype of breast cancer of heterogeneous nature that is negative for estrogen receptor (ER), progesterone receptor (PR) and growth factor human epidermal 2 (HER2) following immunohistochemical analysis. TNBC is frequently characterized by relapse and reduced survival. To date, there is no targeted therapy for this type of cancer. Chemotherapy, radiotherapy, and surgery remain as the standard treatments options. The lack of a target therapy and the heterogeneity of TNBC highlight the need to seek new therapeutic options. In this study, fresh tissue samples of TNBC were analyzed with a panel of 48 driver genes (212 amplicons) that are likely to be therapeutic targets. We found intron variants, missense, stop gained and splicing variants in and genes. Interestingly, all the analyzed samples had at least two variants in the gene, one being a drug response variant, rs1042522, found in 94% of our samples. We also found seven additional variants not previously reported in the gene, to the best of our knowledge, with probable deleterious characteristics of the tumor suppressor gene. We found four genetic variants in the gene, including two missense variants. The rs2491231 variant in the gene was identified in 84% (16/19) of the samples, which not yet reported for TNBC, to the best of our knowledge. In conclusion, genetic variants in were found in all TNBC tumors, with rs1042522 being the most frequent (94% of TNBC biopsies), which had not been previously reported in TNBC. Also, we found two missense variants in the gene. These results justify the validation of these genetic variants in a large cohort, as well as the extensive study of their impact on the prognosis and therapy management of TBNC.
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http://dx.doi.org/10.3892/ol.2019.9984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396222PMC
March 2019

Genomic surveillance links livestock production with the emergence and spread of multi-drug resistant non-typhoidal Salmonella in Mexico.

J Microbiol 2019 Apr 5;57(4):271-280. Epub 2019 Feb 5.

Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City, Mexico.

Multi-drug resistant (MDR) non-typhoidal Salmonella (NTS) is increasingly common worldwide. While food animals are thought to contribute to the growing antimicrobial resistance (AMR) problem, limited data is documenting this relationship, especially in low and middle-income countries (LMIC). Herein, we aimed to assess the role of non-clinical NTS of bovine origin as reservoirs of AMR genes of human clinical significance. We evaluated the phenotypic and genotypic AMR profiles in a set of 44 bovine-associated NTS. For comparative purposes, we also included genotypic AMR data of additional isolates from Mexico (n = 1,067) that are publicly available. The most frequent AMR phenotypes in our isolates involved tetracycline (40/44), trimethoprim-sulfamethoxazole (26/44), chloramphenicol (19/44), ampicillin (18/44), streptomycin (16/44), and carbenicillin (13/44), while nearly 70% of the strains were MDR. These phenotypes were correlated with a widespread distribution of AMR genes (i.e. tetA, aadA, dfrA12, dfrA17, sul1, sul2, bla-TEM-1, blaCARB-2) against multiple antibiotic classes, with some of them contributed by plasmids and/or class-1 integrons. We observed different AMR genotypes for betalactams and tetracycline resistance, providing evidence of convergent evolution and adaptive AMR. The probability of MDR genotype occurrence was higher in meat-associated isolates than in those from other sources (odds ratio 11.2, 95% confidence interval 4.5-27.9, P < 0.0001). The study shows that beef cattle are a significant source of MDR NTS in Mexico, highlighting the role of animal production on the emergence and spread of MDR Salmonella in LMIC.
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http://dx.doi.org/10.1007/s12275-019-8421-3DOI Listing
April 2019

Evaluation of skin expression profiles of patients with vitiligo treated with narrow-band UVB therapy by targeted RNA-seq.

An Bras Dermatol 2018 Nov/Dec;93(6):843-851

Department of Biochemistry and Molecular Medicine, Facultad de Medicina, Universidad Autónoma de Nuevo León, Nuevo León, México.

Background: Vitiligo is characterized by a lack of pigmentation in the skin. To date, there are no studies that analyze the changes in gene expression in the skin of vitiligo patients in response to narrow-band ultraviolet B (nb-UVB) phototherapy treatment.

Objective: Explore the usefulness of new generation RNA sequencing in the identification of gene expression changes in the skin of vitiligo patients treated with nb-UVB phototherapy.

Methods: Four skin biopsies (4mm in diameter) were collected from 45 Mexican vitiligo vulgaris patients, 2 specimens before and 2 after treatment with nb-UVB phototherapy, obtained from pigmented and non-pigmented tissue. RNA extracted from the biopsies was analyzed using the Illumina TruSeq Targeted RNA Expression protocol to study the expression of genes that participate in pathways of skin homeostasis. The 2 groups were compared using Student's t-test and the Mann-Whitney U-test.

Results: The expression analysis identified differences in 12 genes included in this study after comparing the samples obtained before and after treatment: 5 genes involved in skin pigmentation, 2 genes involved in apoptosis, 2 genes involved in cell survival, 2 genes involved in oxidative stress responses and 1 gene involved in signal transduction mechanisms (p<0.05).

Study Limitations: The small size of skin biopsies limits the amount of RNA obtained, the number of genes to be analyzed and the use of conventional techniques such as RT-qPCR.

Conclusion: We demonstrated usefulness of new generation RNA sequencing in the identification of gene expression changes, in addition to identifying new targets in the study of vitiligo.
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http://dx.doi.org/10.1590/abd1806-4841.20187589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256230PMC
February 2019

Evaluation of the Expression of Genes Associated with Inflammation and Apoptosis in Androgenetic Alopecia by Targeted RNA-Seq.

Skin Appendage Disord 2018 Oct 7;4(4):268-273. Epub 2017 Dec 7.

Centro de Investigación y Desarrollo en Ciencias de la Salud, UANL, Mexico.

Androgenetic alopecia (AGA) or male pattern baldness is the most common form of hair loss in humans. Despite being a very frequent dermatological entity, molecular pathophysiology remains unclear. Several authors relate the presentation of AGA with a premature apoptotic process during the anagen phase and with an inflammatory microenvironment in the hair follicle. We evaluated a panel of 30 genes associated with inflammation and apoptosis in 5 AGA patients by targeted RNA-Seq. gene was highly expressed in patients in stages 3V to 5 on the Hamilton-Norwood scale compared to patients with 5A stage. and genes were overexpressed in stages 3V and 4 compared to stages 5 and 5A. Overexpression of these genes detected only at early stages of AGA proves the role of WNT pathway, apoptosis, and inflammation in the development of this disorder.
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http://dx.doi.org/10.1159/000484530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219216PMC
October 2018

A solitary presentation of panniculitis in a patient with a history of breast cancer.

Ann Med Surg (Lond) 2018 Dec 17;36:54-57. Epub 2018 Oct 17.

Tecnologico de Monterrey, Hospital San Jose, Servicio de Patologia, Mexico.

Introduction: Panniculits presents as an inflammation of the subcutaneous adipose tissue of the skin. In breast, panniculitis is very rare and is usually a manifestation of underlying inflammatory conditions. The typical presentation is palpable tender nodules, which in cases of breast panniculitis, triggers an extensive work up to exclude a malignancy. Herein we present a case of septal and lobar panniculitis in a female with clinical history of invasive ductal carcinoma.

Presentation Of The Case: A 52-year old female with past medical history of invasive breast carcinoma 5 years prior to the presentation. The patient's chief complaint was a 1-year history of a subcutaneous nodular lesion on her left breast. A core biopsy of the firm nodule showed marked inflammation of the breast. A second skin biopsy showed an abundant chronic inflammatory infiltrate, with lymphocytic vasculitis and neuritis, suggestive of an underlying autoimmune process.

Discussion: Subcutaneous panniculitis with or without vasculitis is a rare condition when presenting in the breast. Panniculitis can mimic malignancy and thus, it is important to differentially diagnose it from breast carcinoma. Histologically, it is classified in lobular and septal lymphocytic panniculitis depending on specific diagnostic characteristics.

Conclusion: Panniculitis of the breast is a rare condition that needs to be included in the differential diagnosis of subcutaneous breast masses. In all cases, but specifically in females with history of breast cancer, panniculitis still should be thought of as a possibility, and imaging as well as other diagnostic techniques can aid in making the correct diagnosis.
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http://dx.doi.org/10.1016/j.amsu.2018.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206327PMC
December 2018

Pure mucinous breast carcinoma in a 25-year-old female, a case report.

Int J Surg Case Rep 2018 17;53:58-60. Epub 2018 Oct 17.

Tecnologico de Monterrey, Hospital San Jose, Servicio de Patología, Mexico; UANL, Facultad de Medicina, Hospital Universitario, Mexico. Electronic address:

Introduction: Mucinous carcinoma is a variant of invasive breast carcinomas representing 2% of them. These tumors frequently develop in postmenopausal females; it is a rare histological variant in young patients.

Case Presentation: A 25-year-old female refers a slow growth mass of 2 years of evolution. Excisional biopsy reveals a pure mucinous carcinoma with positive hormone receptors and negative HER2. She was treated with hormone therapy and surgical resection.

Discussion: Mucinous carcinoma is a rare variant reported in young patients. Many series report that is frequently found in postmenopausal patients. We present a case of a pure mucinous carcinoma in a 25-year-old female with the importance of being a low-frequency malignancy in young patients.

Conclusion: Due to its benign course, it is important to know that this lesion can also present in young patients. The importance underlies in the multidisciplinary management at the right time in a proper way.
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http://dx.doi.org/10.1016/j.ijscr.2018.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218698PMC
October 2018

Infection and coinfection by human papillomavirus, Epstein-Barr virus and Merkel cell polyomavirus in patients with squamous cell carcinoma of the larynx: a retrospective study.

PeerJ 2018 24;6:e5834. Epub 2018 Oct 24.

Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México.

Background: Human papillomavirus (HPV) is recognized as an important risk factor for laryngeal carcinogenesis. Although HPV-16 and 18 have been strongly implicated, the presence of other high-risk HPV (HR-HPV) genotypes or the coinfection with Epstein-Barr virus (EBV) or Merkel cell polyomavirus (MCPV) may increase the risk, but their etiological association has not been definitively established.

Methods: We characterized the genotype-specific HPV and the frequency of EBV and MCPV infections through the detection of their DNA in 195 laryngeal specimens of squamous cell carcinoma (SCC) histologically confirmed.

Results: HPV DNA was detected in 93 (47.7%) specimens. HPV-11 was the most frequent with 68 cases (73.1%), and HPV-52 was the most frequently HR-HPV found with 51 cases, which corresponds to 54.8% of all HPV-positive specimens. EBV DNA was detected in 54 (27.7%) tumor tissue specimens of which 25 (46.3%) were in coinfection with HPV. MCPV DNA was detected only in 11 (5.6%) cases of which 5 (45.4%) were in coinfection with an HR-HPV. No association between the presence of DNA of the three examined viruses and the patient smoking habits, alcohol consumption, age, the keratinization status, differentiation grade, or localization of the tumor in the larynx were found.

Discussion: HPV-52 was the most prevalent HR-HPV, which may suggest that this and other genotypes in addition to HPV-16 and 18 could be considered for prophylaxis. However, further studies including non-cancer larynx cases and the evaluation of other molecular markers and viral co-infection mechanisms are needed to determine the role of the different HR-HPV genotypes, EBV, and MCPV in the etiology of SCC of the larynx.
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http://dx.doi.org/10.7717/peerj.5834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203941PMC
October 2018

Interethnic Variability in CYP2D6, CYP2C9, and CYP2C19 Genes and Predicted Drug Metabolism Phenotypes Among 6060 Ibero- and Native Americans: RIBEF-CEIBA Consortium Report on Population Pharmacogenomics.

OMICS 2018 09 11;22(9):575-588. Epub 2018 Sep 11.

1 RIBEF Ibero-American Network of Pharmacogenetics and Pharmacogenomics , Badajoz, Spain .

Pharmacogenetic variation in Latin Americans is understudied, which sets a barrier for the goal of global precision medicine. The RIBEF-CEIBA Network Consortium was established to characterize interindividual and between population variations in CYP2D6, CYP2C9, and CYP2C19 drug metabolizing enzyme genotypes, which were subsequently utilized to catalog their "predicted drug metabolism phenotypes" across Native American and Ibero American populations. Importantly, we report in this study, a total of 6060 healthy individuals from Ibero-America who were classified according to their self-reported ancestry: 1395 Native Americans, 2571 Admixed Latin Americans, 96 Afro-Latin Americans, 287 white Latin Americans (from Cuba), 1537 Iberians, and 174 Argentinean Ashkenazi Jews. Moreover, Native Americans were grouped into North-, Central-, and South Amerindians (from Mexico, Costa Rica, and Peru, respectively). All subjects were studied for the most common and functional CYP2D6, CYP2C9, and CYP2C19 allelic variants, and grouped as genotype-predicted poor or ultrarapid metabolizer phenotypes (gPMs and gUMs, respectively). Native Americans showed differences from each ethnic group in at least two alleles of CYP2D6, CYP2C9, and CYP2C19. Native Americans had higher frequencies of wild-type alleles for all genes, and lower frequency of CYP2D6*41, CYP2C9*2, and CYP2C19*17 (p < 0.05). Native Americans also showed less CYP2C19 gUMs than the rest of the population sample. In addition, differences within Native Americans (mostly North vs. South) were also found. The interethnic differences described supports the need for population-specific personalized and precision medicine programs for Native Americans. To the best of our knowledge, this is the largest study carried out in Native Americans and other Ibero-American populations analyzing CYP2D6, CYP2C9, and CYP2C19 genetic polymorphisms. Population pharmacogenomics is a nascent field of global health and warrants further research and education.
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http://dx.doi.org/10.1089/omi.2018.0114DOI Listing
September 2018

Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring.

Nutr Metab (Lond) 2018 5;15:38. Epub 2018 Jun 5.

1Departmento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico.

Background: Maternal overnutrition including pre-pregnancy, pregnancy and lactation promotes a lipotoxic insult leading to metabolic dysfunction in offspring. Diet-induced obesity models (DIO) show that changes in hypothalamic mitochondria fusion and fission dynamics modulate metabolic dysfunction. Using three selective diet formula including a High fat diet (HFD), Cafeteria (CAF) and High Sugar Diet (HSD), we hypothesized that maternal diets exposure program leads to selective changes in hypothalamic mitochondria fusion and fission dynamics in male offspring leading to metabolic dysfunction which is exacerbated by a second exposure after weaning.

Methods: We exposed female Wistar rats to nutritional programming including Chow, HFD, CAF, or HSD for 9 weeks (pre-mating, mating, pregnancy and lactation) or to the same diets to offspring after weaning. We determined body weight, food intake and metabolic parameters in the offspring from 21 to 60 days old. Hypothalamus was dissected at 60 days old to determine mitochondria-ER interaction markers by mRNA expression and western blot and morphology by transmission electron microscopy (TEM). Mitochondrial-ER function was analyzed by confocal microscopy using hypothalamic cell line mHypoA-CLU192.

Results: Maternal programming by HFD and CAF leads to failure in glucose, leptin and insulin sensitivity and fat accumulation. Additionally, HFD and CAF programming promote mitochondrial fusion by increasing the expression of MFN2 and decreasing DRP1, respectively. Further, TEM analysis confirms that CAF exposure after programing leads to an increase in mitochondria fusion and enhanced mitochondrial-ER interaction, which partially correlates with metabolic dysfunction and fat accumulation in the HFD and CAF groups. Finally, we identified that lipotoxic palmitic acid stimulus in hypothalamic cells increases Ca overload into mitochondria matrix leading to mitochondrial dysfunction.

Conclusions: We concluded that maternal programming by HFD induces hypothalamic mitochondria fusion, metabolic dysfunction and fat accumulation in male offspring, which is exacerbated by HFD or CAF exposure after weaning, potentially due to mitochondria calcium overflux.
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http://dx.doi.org/10.1186/s12986-018-0279-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987395PMC
June 2018

Whole genome sequencing reveals widespread distribution of typhoidal toxin genes and VirB/D4 plasmids in bovine-associated nontyphoidal Salmonella.

Sci Rep 2018 06 29;8(1):9864. Epub 2018 Jun 29.

Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico.

Nontyphoidal Salmonella (NTS) is a common pathogen in food-producing animals and a public health concern worldwide. Various NTS serovars may be present in apparently healthy animals. This could result in carcass contamination during the slaughter process leading to human exposure. While most genomic research has focused on Salmonella pathogenesis, little is known on the factors associated with subclinical infections and environmental persistence. We report here the widespread distribution of typhoidal toxin genes (i. e. the cdtB islet, hlyE, taiA), among NTS strains from a beef slaughter operation (n = 39) and from epidemiologically unconnected ground beef (n = 20). These genes were present in 76% of the strains, regardless of serovar, isolation source or geographical location. Moreover, strains that predominated in the slaughterhouse carry plasmid-borne type IV secretion systems (T4SS), which have been linked to persistent infections in numerous pathogens. Population genomics supports clonal dissemination of NTS along the food production chain, highlighting its role as reservoir of genetic variability in the environment. Overall, the study provides a thorough characterization of serovar diversity and genomic features of beef-associated NTS in Mexico. Furthermore, it reveals how common genetic factors could partially explain the emergence and persistence of certain NTS serovars in the beef industry.
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http://dx.doi.org/10.1038/s41598-018-28169-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026178PMC
June 2018

Uridine 5'-diphospho-glucronosyltrasferase: Its role in pharmacogenomics and human disease.

Exp Ther Med 2018 Jul 18;16(1):3-11. Epub 2018 May 18.

Tecnologico de Monterrey, Medical School and Health Sciences, Monterrey, Nuevo Leon 64710, Mexico.

Biotransformation is an enzyme-catalyzed process in which the body converts endogenous compounds, xenobiotics and toxic substances into harmless or easily excreted metabolites. The biotransformation reactions are classified as phase I and II reactions. Uridine 5'-diphospho (UDP)-glucuronosyltransferases (UGTs) are a superfamily of phase II enzymes which have roles in the conjugation of xenobiotics or endogenous compounds, including drugs and bilirubin, with glucuronic acid to make them easier to excrete. The method the human body uses to achieve glucuronidation may be affected by a large interindividual variation due to changes in the sequences of the genes encoding these enzymes. In the last five years, the study of the genetic variants of the UGTs at a molecular level has become important due to its association with several diseases and the ability to predict adverse events due to drug metabolism. In the present review, the structure and the prominent genetic variants of the UGT1A subfamily and their metabolic and clinical implications are described.
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http://dx.doi.org/10.3892/etm.2018.6184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995049PMC
July 2018

Tyrphostin AG17 inhibits adipocyte differentiation in vivo and in vitro.

Lipids Health Dis 2018 May 29;17(1):128. Epub 2018 May 29.

Unidad de Genómica, UANL, CIDICS, Monterrey, Mexico.

Background: Excessive subcutaneous adiposity in obesity is associated to positive white adipocyte tissue (WAT) differentiation (adipogenesis) and WAT expandability. Here, we hypothesized that supplementation with the insulin inhibitor and mitochondrial uncoupler, Tyrphostin (T-AG17), in vitro and in vivo inhibits adipogenesis and adipocyte hypertrophy.

Methods: We used a 3T3-L1 proadipocyte cell line to identify the potential effect of T-AG17 on adipocyte differentiation and fat accumulation in vitro. We evaluated the safety of T-AG17 and its effects on physiological and molecular metabolic parameters including hormonal profile, glucose levels, adipogenesis and adipocyte hypertrophy in a diet-induced obesity model using C57BL/6 mice.

Results: We found that T-AG17 is effective in preventing adipogenesis and lipid synthesis in the 3T3-L1 cell line, as evidenced by a significant decrease in oil red staining (p < 0.05). In obese C57BL/6 mice, oral administration of T-AG17 (0.175 mg/kg for 2 weeks) lead to decreased fat accumulation and WAT hypertrophy. Further, T-AG17 induced adipocyte apoptosis by activating caspase-3. In the hepatocytes of obese mice, T-AG17 promoted an increase in the size of lipid inclusions, which was accompanied by glycogen accumulation. T-AG17 did not alter serum biochemistry, including glucose, insulin, leptin, free fatty acids, creatinine, and aspartate aminotransferase.

Conclusion: T-AG17 promotes adipocyte apoptosis in vivo and is an effective modulator of adipocyte differentiation and WAT hypertrophy in vitro and in vivo. Therefore, T-AG17 may be useful as a pharmacological obesity treatment.
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http://dx.doi.org/10.1186/s12944-018-0784-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975476PMC
May 2018

Comparison of specific expression profile in two hypoxia models.

Exp Ther Med 2018 Jun 10;15(6):4777-4784. Epub 2018 Apr 10.

Center for Research and Development in Health Sciences, Genomic Unit, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo León 64460, Mexico.

The microenvironment plays a fundamental role in carcinogenesis: Acidity and hypoxia are actively involved in this process. It is important to have models to study these mechanisms. The models that are most commonly referred to are the hypoxia chamber and the chemical induction [Cobalt (II) chloride]. It is not yet defined if these models are interchangeable if the metabolic effect is the same, and if the results may be compared in these models. In the present study, the response to the effect of stress (hypoxia and acidity) in both models was evaluated. The results indicated that in the chemical model, the effect of hypoxia appeared in an early form at 6 h; whereas in the gas chamber the effect was slow and gradual and at 72 h there was an overexpression of erythropoietin (), vascular endothelial growth factor (), carbonic anhydrase 9 () and hypoxia-inducible factor 1α (). In addition to the genes analyzed by reverse transcription-quantitative polymerase chain reaction, the global expression analysis between both models revealed the 9 most affected genes in common. The present study additionally identified 3 potential genes (lysyl oxidase, ankyrin repeat domain 37, B-cell lymphoma 2 interacting protein 3 like) previously identified in other studies, which may be considered as universal hypoxia genes along with , glucose transporter 1 (), , and . To the best of the author's knowledge, this is the first time that both hypoxia models have been compared, and it was demonstrated that the effect of hypoxia induction was time sensitive in each model. These observations must be considered prior to selecting one of these models to identify selective hypoxia genes and their effects in cancer.
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http://dx.doi.org/10.3892/etm.2018.6048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958671PMC
June 2018

Genetic and molecular aspects of androgenetic alopecia.

Indian J Dermatol Venereol Leprol 2018 May-Jun;84(3):263-268

Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico.

Androgenetic alopecia is the most common form of progressive hair loss in humans. A genetic predisposition and hormonal status are considered as major risk factors for this condition. Several recent advances in molecular biology and genetics have increased our understanding of the mechanisms of hair loss in androgenetic alopecia. We review these advances and examine the trends in the genetic and molecular aspects of androgenetic alopecia.
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http://dx.doi.org/10.4103/ijdvl.IJDVL_262_17DOI Listing
September 2018

Microsatellite instability and protein expression of and genes in young Mexican patients less than 50 years of age diagnosed with colorectal cancer.

Int J Clin Exp Pathol 2018 1;11(3):1667-1673. Epub 2018 Mar 1.

Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autonoma de Nuevo Leon Mexico.

Diagnosis of colorectal cancer in patients under 45 years old should alert us to possible hereditary forms of this neoplasia. Most cases of hereditary colorectal cancer correspond to Lynch syndrome which is caused by mutations in DNA mismatch repair genes, particularly and . The dysfunction is associated with microsatellite instability which occurs in 95% cases of this syndrome and in 15% of sporadic colorectal cancer. In sporadic colon tumors, downregulation of is observed in cases with the V600E variant, which induces hypermetylation of the promoter. Mutation screening for hereditary cancer has impacted the diagnosis, genetic counseling, and early tumor detection in families affected by hereditary colorectal cancer syndromes but mutation screening technologies are seldom available in public health care centers in developing countries. This study aimed to describe immunohistochemistry and microsatellite instability abnormalities in tumor samples archived in a public hospital in Mexico. Paraffin-embedded samples of patients with colorectal cancer, diagnosed at under 50 years old, were studied to analyze correlations among clinical variables, MLH1 and MSH2 protein expression (immunohistochemistry), microsatellite instability (fluorescent PCR-based assay), and V600E variant (real time PCR). Forty-seven tumor specimens from patients with TNM stage II and above were analyzed. Tumors were mainly located in the proximal colon segment and displayed histologic intestinal variety and infiltration to serosa. Twenty samples showed decreased expression of mismatch repair proteins and 10 of these presented microsatellite instability (7 high and 3 low instability patterns, respectively). There were no instances of V600E mutation found. Altered or expression was found in 42.5% of the samples and microsatellite instability was observed in 21.3% of the tumors. These results suggested that about a fifth of the patients were candidates for family assessment and genetic counseling.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958109PMC
March 2018

CAPN3, DCT, MLANA and TYRP1 are overexpressed in skin of vitiligo vulgaris Mexican patients.

Exp Ther Med 2018 Mar 17;15(3):2804-2811. Epub 2018 Jan 17.

Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, México.

Vitiligo is a disorder causing skin depigmentation, in which several factors have been proposed for its pathogenesis: Environmental, genetic and biological aspects of melanocytes, even those of the surrounding keratinocytes. However, the lack of understanding of the mechanisms has complicated the task of predicting the development and progression. The present study used microarray analysis to characterize the transcriptional profile of skin from Vitiligo Vulgaris (VV) patients and the identified transcripts were validated using targeted high-throughput RNA sequencing in a broader set of patients. For microarrays, mRNA was taken from 20 skin biopsies of 10 patients with VV (pigmented and depigmented skin biopsy of each), and 5 biopsies of healthy subjects matched for age and sex were used as a control. A signature was identified that contains the expression pattern of 722 genes between depigmented vitiligo skin vs. healthy control, 1,108 between the pigmented skin of vitiligo vs. healthy controls and 1,927 between pigmented skin, depigmented vitiligo and healthy controls (P<0.05; false discovery rate, <0.1). When comparing the pigmented and depigmented skin of patients with vitiligo, which reflects the real difference between both skin types, 5 differentially expressed genes were identified and further validated in 45 additional VV patients by RNA sequencing. This analysis showed significantly higher RNA levels of calpain-3, dopachrome tautomerase, melan-A and tyrosinase-related protein-1 genes. The data revealed that the pigmented skin of vitiligo is already affected at the level of gene expression and that the main differences between pigmented and non-pigmented skin are explained by the expression of genes associated with pigment metabolism.
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http://dx.doi.org/10.3892/etm.2018.5764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795480PMC
March 2018

Thymidylate synthase gene variants as predictors of clinical response and toxicity to fluoropyrimidine-based chemotherapy for colorectal cancer.

Drug Metab Pers Ther 2017 12;32(4):209-218

Universidad Autonoma de Nuevo Leon, Center for Research and Development in Health Sciences, Monterrey, Mexico.

Background: Fluoropyrimidines form the chemotherapy backbone of advanced and metastatic colorectal cancer (CRC). These drugs are frequently associated with toxicity events that result in dose adjustments and even suspension of the treatment. The thymidylate synthase (TYMS) gene is a potential marker of response and toxicity to fluoropyirimidines as this enzyme is the molecular target of these drugs. Our aim was to assess the association between variants of TYMS with response and toxicity to fluoropyrimidines in patients with CRC in independent retrospective and prospective studies.

Methods: Variants namely rs45445694, rs183205964, rs2853542 and rs151264360 of TYMS were genotyped in 105 CRC patients and were evaluated to define their association with clinical response and toxicity to fluoropyrimidines. Additionally, the relationship between genotypes and tumor gene expression was analyzed by quantitative polymerase chain reaction.

Results: The 2R/2R (rs45445694) was associated with clinical response (p=0.05, odds ratio (OR)=3.45) and severe toxicity (p=0.0014, OR=5.21, from pooled data). Expression analysis in tumor tissues suggested a correlation between the 2R/2R genotype and low TYMS expression.

Conclusions: The allele 2R (rs45445694) predicts severe toxicity and objective response in advanced CRC patients. In addition, the alleles G(rs2853542) and 6bp-(rs151264360) are independent predictors of response failure to chemotherapy. This is the first study made on a Latin American population that points out TYMS gene variants have predictive values for response and toxicity in patients with CRC treated with fluoropyrimidine-based chemotherapy.
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http://dx.doi.org/10.1515/dmpt-2017-0028DOI Listing
December 2017

Modular organization of a hypocretin gene minimal promoter.

Mol Med Rep 2018 Feb 22;17(2):2263-2270. Epub 2017 Nov 22.

Department of Basic Science, School of Health Sciences, Universidad de Monterrey, San Pedro Garzia, NL 66238, Mexico.

Orexins or hypocretins are neurotransmitters produced by a small population of neurons in the lateral hypothalamus. This family of peptides modulates sleep‑wake cycle, arousal and feeding behaviors; however, the mechanisms regulating their expression remain to be fully elucidated. There is an interest in defining the key molecular elements in orexin regulation, as these may serve to identify targets for generating novel therapies for sleep disorders, obesity and addiction. Our previous studies showed that the expression of orexin was decreased in mice carrying null‑mutations of the transcription factor early B‑cell factor 2 (ebf2) and that the promoter region of the prepro‑orexin (Hcrt) gene contained two putative ebf‑binding sites, termed olf‑1 sites. In the present study, a minimal promoter region of the murine Hcrt gene was identified, which was able to drive the expression of a luciferase reporter gene in the human 293 cell line. Deletion of the olf1‑site proximal to the transcription start site of the Hcrt gene increased reporter gene expression, whereas deletion of the distal olf1‑like site decreased its expression. The lentiviral transduction of murine transcription factor ebf2 cDNA into 293 cells increased the gene expression driven by this minimal Hcrt‑gene promoter and an electrophoretic mobility shift assays demonstrated that the distal olf1‑like sequence was a binding site for ebf2.
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http://dx.doi.org/10.3892/mmr.2017.8142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783473PMC
February 2018