Molecular Bases of Protein Antigenicity and Determinants of Immunogenicity, Anergy, and Mitogenicity.

BACKGROUND: The immune system is able to recognize substances that originate from inside or outside the body and are potentially harmful. Foreign substances that bind to immune system components exhibit antigenicity and are defined as antigens. The antigens exhibiting immunogenicity can induce innate or adaptive immune responses and give rise to humoral or cell-mediated immunity. The antigens exhibiting mitogenicity can cross-link cell membrane receptors on B and T lymphocytes leading to cell proliferation. All antigens vary greatly in physicochemical features such as biochemical nature, structural complexity, molecular size, foreignness, solubility, and so on. OBJECTIVE: Thus, this review aims to describe the molecular bases of protein-antigenicity and those molecular bases that lead to an immune response, lymphocyte proliferation, or unresponsiveness. CONCLUSION: The epitopes of an antigen are located in surface areas; they are about 880-3,300 Da in size. They are protein, carbohydrate, or lipid in nature. Soluble antigens are smaller than 1 nm and are endocytosed less efficiently than particulate antigens. The more the structural complexity of an antigen increases, the more the antigenicity increases due to the number and variety of epitopes. The smallest immunogens are about 4,000-10,000 Da in size. The more phylogenetically distant immunogens are from the immunogen-recipient, the more immunogenicity increases. Antigens that are immunogens can trigger an innate or adaptive immune response. The innate response is induced by antigens that are pathogen-associated molecular patterns. Exogenous antigens, T Dependent or T Independent, induce humoral immunogenicity. TD protein-antigens require two epitopes, one sequential and one conformational to induce antibodies, whereas, TI non-protein-antigens require only one conformational epitope to induce low-affinity antibodies. Endogenous protein antigens require only one sequential epitope to induce cell-mediated immunogenicity.

NUSAP1 and PCLAF (KIA0101) Downregulation by Neoadjuvant Therapy is Associated with Better Therapeutic Outcomes and Survival in Breast Cancer.

Purpose: To evaluate whether changes in genomic expression that occur beginning with breast cancer (BC) diagnosis and through to tumor resection after neoadjuvant chemotherapy (NCT) reveal biomarkers that can help predict therapeutic response and survival. Materials and Methods: We determined gene expression profiles based on microarrays in tumor samples from 39 BC patients who showed pathologic complete response (pCR) or therapeutic failure (non-pCR) after NCT (cyclophosphamide-doxorubicin/epirubicin). Based on unsupervised clustering of gene expression, together with functional enrichment analyses of differentially expressed genes, we selected NUSAP1, PCLAF, MME, and DST. We evaluated the NCT response and the expression of these four genes in BC histologic subtypes. In addition, we study the presence of tumor-infiltrating lymphocytes. Finally, we analyze the correlation between NUSAP1 and PCLAF against disease-free survival (DFS) and overall survival (OS). Results: A signature of 43 differentially expressed genes discriminated pCR from non-pCR patients (|fold change >2|, false discovery rate <0.05) only in biopsies taken after surgery. Patients achieving pCR showed downregulation of NUSAP1 and PCLAF in tumor tissues and increased DFS and OS, while overexpression of these genes correlated with poor therapeutic response and OS. These genes are involved in the regulation of mitotic division. Conclusions: The downregulation of NUSAP1 and PCLAF after NCT is associated with the tumor response to chemotherapy and patient survival.

Cáncer colorrectal. Variantes génicas en la vía de señalización BMP y ancestría en población mexicana / Colorectal cancer. Genetic variants in BMP signaling pathway and ancestry in the Mexican population

Resumen Introducción: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. Objetivo: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoamericana y caucásica. Métodos: Se realizó el genotipado de 1000 casos de cáncer colorrectal y 1043 individuos de control reclutados en la Ciudad de México, Monterrey y Torreón mediante la plataforma Sequenom. Con análisis univariados y multivariados se estudiaron las asociaciones entre cáncer colorrectal y variantes. Resultados: Las variantes rs4444235, rs12953717 y rs4939827 replicaron la asociación con la neoplasia (p ≤ 0.05). La ascendencia caucásica mostró asociación con el tumor. Conclusiones: El estudio mostró las asociaciones entre cáncer colorrectal y las variantes SMAD7 y BMP4, así como con el componente caucásico de la mezcla étnica.

Abstract Introduction: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. Objective: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous American and Caucasian ancestry. Methods: Genotyping of 1,000 colorectal cancer cases and 1,043 control individuals recruited in Mexico City, Monterrey, and Torreón was carried out using the Sequenom platform. Associations between colorectal cancer and variants were studied with univariate and multivariate analyses. Results: Variants rs4444235, rs12953717 and rs4939827 replicated the association with the neoplasm (p ≤ 0.05). Caucasian ancestry showed association with the tumor. Conclusions: The study replicated the associations between colorectal cancer and SMAD7 and BMP4 variants, with an association being observed with the Caucasian component of the ethnic mix.

Tannic Acid, as a Structural Moiety Coupled to a Protein Antigen, Exhibiting a Molecular-structure Adjuvant Activity for Antibody Specificity Enhancement.

BACKGROUND: An antigen is a small foreign substance, such as a microorganism structural protein, that may trigger an immune response once inside the body. Antigens are preferentially used rather than completely attenuated microorganisms to develop safe vaccines. Unfortunately, not all antigens are able to induce an immune response. Thus, new adjuvants to enhance the antigen's ability to stimulate immunity must be developed. OBJECTIVES: Therefore, this work aimed to evaluate the molecular-structure adjuvant activity of tannic acid (TA) coupled to a protein antigen in Balb/c mice. METHODS: Bovine serum albumin (BSA) was used as an antigen. The coupling of BSA and TA was mediated by carbodiimide crosslinking, and verified by SDS-PAGE. Forty-two Balb/c mice were divided into seven groups, including two controls without antigen, an antigen control, an adjuvant control, and two treatment groups. An additional group was used for macrophages isolation. A 30-day scheme was used to immunize the mice. The analysis of humoral immunity included immunoglobulin quantification, isotyping and antigen-antibody precipitation. The analysis of cell-mediated immunity included the quantification of nitric oxide from peritoneal macrophages and splenocytes' proliferation assay after treatment stimulation. RESULTS: No differences were found in the antibodies' concentration or isotypes induced with the conjugate or the pure BSA. However, an immunogenicity improvement (p < 0.05) was observed through the specific anti-BSA antibody titers in mice immunized with the conjugate. Besides, macrophage activation (p < 0.05) was detected when stimulated with the treatments containing TA. CONCLUSION: Tannic acid exhibited macrophages' activation properties. Moreover, when TA was incorporated into the structure of a protein antigen, such as BSA, an antibody specificity enhancement was observed. This was a consequence of antigen processing by activated antigen-presenting cells. These results showed the use of tannic acid as a novel candidate for vaccine molecular-structure adjuvant.

Survivin in Breast Cancer: A Review.

Breast cancer is the most frequently diagnosed cancer in women and ranks second among causes for cancer-related death in women. Gene technology has led to the recognition that breast cancer is a heterogeneous disease composed of different biological subtypes, and genetic profiling enables the response to chemotherapy to be predicted. This fact emphasizes the importance of selecting sensitive diagnostic and prognostic markers in the early disease stage and more efficient targeted treatments for this disease. One such prognostic marker appears to be survivin. Many studies have shown that survivin is strongly expressed in different types of cancers. Its overexpression has been demonstrated in breast cancer, and high activity of the survivin gene has been associated with a poor prognosis and worse survival rates.

Role of ß-Klotho and Malondialdehyde in Metabolic Disorders, HIV Infection, and Antiretroviral Therapy.

Metabolic alterations, resulting from factors such as obesity or infections (HIV), generate inflammation in the body, affecting the immune system and causing oxidative stress. Prolonged exposure to antiretroviral therapy (ART) conditions the appearance of alterations considered risk factors for metabolic syndrome (MetS), affecting the quality of life in people living with HIV/AIDS (PLWHA). ß-klotho is a protein that can counteract levels of oxidative stress. The aim was to determine the relation of ß-klotho and oxidative stress with metabolic alterations in PLWHA. We hypothesized that levels of ß-klotho and malondialdehyde (MDA) are related in PLWHA on ART with overweight/obesity. As a result of comparing cases versus controls, significant differences were obtained in levels of ß-klotho (p = 0.011), MDA (p < 0.0001), body mass index (p = 0.001), and weight (p < 0.0001). The presence of MetS in PLWHA was 21.2% and 10.6% according to the World Health Organization and ATP III (National Cholesterol Education Program Adult Treatment Panel III) criteria, respectively. The founded correlations were of ß-klotho (r = 0.019) and MDA (r = 0.0001), both with CD4+ cells in PLWHA. In controls, ß-klotho was correlated with very low-density lipoprotein (r = 0.035) and atherogenic index (AI; r = 0.037), MDA with AI (r = 0.039), cholesterol, and low-density lipoprotein (r = 0.002). The increase of inflammation in the organism, owing to HIV infection and/or the presence of obesity, conditions metabolic disruption or depletion of elements needed for homeostasis in the human body.

Colorectal cancer. Genetic variants in BMP signaling pathway and ancestry in the Mexican population.

INTRODUCTION: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. OBJECTIVE: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous American and Caucasian ancestry. METHODS: Genotyping of 1,000 colorectal cancer cases and 1,043 control individuals recruited in Mexico City, Monterrey, and Torreón was carried out using the Sequenom platform. Associations between colorectal cancer and variants were studied with univariate and multivariate analyses. RESULTS: Variants rs4444235, rs12953717 and rs4939827 replicated the association with the neoplasm (p ≤ 0.05). Caucasian ancestry showed association with the tumor. CONCLUSIONS: The study replicated the associations between colorectal cancer and SMAD7 and BMP4 variants, with an association being observed with the Caucasian component of the ethnic mix.

INTRODUCCIÓN: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. OBJETIVO: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoamericana y caucásica. MÉTODOS: Se realizó el genotipado de 1000 casos de cáncer colorrectal y 1043 individuos de control reclutados en la Ciudad de México, Monterrey y Torreón mediante la plataforma Sequenom. Con análisis univariados y multivariados se estudiaron las asociaciones entre cáncer colorrectal y variantes. RESULTADOS: Las variantes rs4444235, rs12953717 y rs4939827 replicaron la asociación con la neoplasia (p ≤ 0.05). La ascendencia caucásica mostró asociación con el tumor. CONCLUSIONES: El estudio mostró las asociaciones entre cáncer colorrectal y las variantes SMAD7 y BMP4, así como con el componente caucásico de la mezcla étnica.

FGF21 serum levels are related to insulin resistance, metabolic changes and obesity in Mexican people living with HIV (PLWH).

BACKGROUND: Antiretroviral therapy has significantly improved prognosis in treatment against HIV infection, however, prolonged exposure is associated to cardiovascular diseases, lipodystrophy, type 2 diabetes, insulin resistance, metabolic alteration, as obesity which includes the accumulation of oxidative stress in adipose tissue. FGF21 is a peptide hormone that is known to regulate glucose and lipid metabolism. FGF21 is expressed and secreted primarily in the liver and adipose tissue, promoting oxidation of glucose/fatty acids and insulin sensitivity. Alterations in FGF21 may be associated with the development of insulin resistance, metabolic syndrome and cardiovascular disease. We hypothesized that FGF21 protein levels are associated with metabolic abnormalities, placing special attention to the alterations in relation to the concurrence of overweight/obesity in people living with HIV (PLWH). DESIGN: Serum FGF21 was analyzed in 241 subjects, 160 PLWH and 81 unrelated HIV-uninfected subjects as a control group. Clinical records were consulted to obtain CD4+ cell counting and number of viral RNA copies. Serum FGF21 levels were tested for correlation with anthropometric and metabolic parameters; glucose, cholesterol, HDL, LDL, VLDL, triglycerides, insulin and indexes of atherogenesis and insulin resistance (HOMA). RESULTS: The participants were classified into four groups: (i) PLWH with normal weight, (ii) PLWH with overweight/obesity, (iii) HIV-uninfected with normal weight, and (iv) HIV-uninfected with overweight/obesity. Insulin levels were higher in normal-weight PLWH than in the HIV-uninfected group but not statistically significant, however, for the overweight/obesity PLWH group, insulin levels were significantly higher in comparison with the other three groups (p<0.0001). For FGF21, serum levels were slightly higher in the overweight/obesity groups in both patients and controls. In HIV-infected subjects, FGF21 levels showed a strong positive correlation with triglycerides, insulin levels and insulin resistance with a p-value <0.0001. In the seronegative group, FGF21 was only correlated with weight and waist circumference, showing an important association of FGF21 levels with the degree of obesity of the individuals. CONCLUSION: Insulin resistance and FGF21 elevations were observed in overweight-obese PLWH. FGF21 elevation could be viewed as a compensation mechanism as, in the control group, FGF21 correlations appeared to be confined to weight and waist circumference. This can be explained based on the action of FGF21 promoting the uptake of glucose in adipose tissue. In PLWH, FGF21 was low, possibly as a result of a change in adiposity leading to a metabolic disruption.

Klotho-HIV and Oxidative Stress: The Role of Klotho in Cardiovascular Disease Under HIV Infection-A Review.

Combined antiretroviral therapy has improved quality and life expectancy of people living with human immunodeficiency virus (HIV). However, this therapy increases oxidative stress (OS), which in turn causes alterations in lipid and carbon metabolism, kidney disease, liver cirrhosis, and increased risk of cardiovascular disease. The Klotho gene has been implicated in cardiovascular risk increase. Klotho protein expression at X level decreases the risk of heart disease. HIV-positive people usually present low plasma levels of Klotho; thus, contributing to some extent to an increase in cardiovascular risk for these types of patients, mostly by favoring atherosclerosis. Therefore, our aim is to provide an overview of the effect of OS on Klotho protein and its consequent cardiometabolic alterations in HIV-positive patients on antiretroviral therapy.

Analysis of Polymorphisms in the MATN3 and DOT1L Genes and CTX-II Urinary Levels in Patients with Knee Osteoarthritis in a Northeast Mexican-Mestizo Population.

Aims: To investigate the possible roles of the single nucleotide polymorphisms (SNPs) MATN3 (rs77245812) and DOT1L (rs12982744) with susceptibility to knee osteoarthritis (KOA) among mestizos from the northeast region of Mexico. In addition, we analyzed the relationship of their urinary levels of carboxy terminal telopeptide of collagen type II (CTX-II) and the radiological grade of disease. Materials and Methods: A total of 223 individuals from a Northeast Mexico Mestizo population were included in this study: 110 patients with primary KOA and 113 healthy controls. Genotyping of the MATN3 (rs77245812) and DOT1L (rs12982744) SNPs was performed by real-time polymerase chain reaction. Results: No association was found between the polymorphisms MATN3 (rs77245812), DOT1L (rs12982744), and the risk of developing KOA (odds ratio [OR] = 1.33, 95% confidence interval [CI] = 0.42-6.48, p = 0.621) (OR = 2.03, 95% CI = 0.35-11.5, p = 0.422). However, urinary CTX-II levels were considerably higher by radiographic grade. Conclusions: An increase in CTX-II per radiographic grade was observed in the case group, but no association was found between MATN3 and DOT1L genes and the risk of KOA in Mexican mestizos.

Clinical Profile of Autism Spectrum Disorder in a Pediatric Population from Northern Mexico.

Autism spectrum disorder (ASD) is a neurodevelopmental condition classified based on needs of support, in order to address impairments in the areas of social communication and restricted and repetitive behavior. The aim of this work is to describe the main clinical features of the ASD severity levels in a group of Mexican pediatric patients. The results show firstly that this condition was more frequent in males than females. Secondly, an inverse relationship was found between the intellectual coefficient and the level of severity of the disorder. Thirdly, deficits in social reciprocity and communication were more evident in Level 3, than in Levels 1 and 2, while the difference was less evident in restricted and repetitive patterns of behavior.

Genetic alterations of triple negative breast cancer (TNBC) in women from Northeastern 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 TP53, PIK3CA and FLT3 genes. Interestingly, all the analyzed samples had at least two variants in the TP53 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 TP53 gene, to the best of our knowledge, with probable deleterious characteristics of the tumor suppressor gene. We found four genetic variants in the PIK3CA gene, including two missense variants. The rs2491231 variant in the FLT3 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 TP53 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 PIK3CA 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.

[¿Azitromicina como tratamiento contra Chlamydia trachomatis?]

Azithromycin and doxycycline effectiveness has been demonstrated in the treatment of urogenital chlamydiasis, which has remained unchanged for a long time. Autoinoculation has been proposed as a method of reinfection and persistence of the disease in women and probably also owing to azithromycin pharmacokinetics in this tissue. With the new diagnostic methods and tests of cure, a difference has been demonstrated in favor of doxycycline in the treatment of rectal chlamydiasis Antimicrobial resistance has not played a relevant role since no treatment-resistant strains have been found in vivo. Nevertheless, azithromycin remains a first-choice drug, since it can be administered as a single dose, which favors therapeutic adherence.

Se ha demostrado la efectividad de la azitromicina y la doxiciclina en el tratamiento de la clamidiasis urogenital, lo que se ha mantenido sin cambios por mucho tiempo. Se ha propuesto la autoinoculación como método de reinfección y persistencia de la enfermedad en las mujeres y también debido a la farmacocinética de la azitromicina en este tejido. Con los nuevos métodos diagnósticos y las pruebas de curación se ha comprobado una diferencia a favor de la doxiciclina en el tratamiento de la clamidiasis rectal. La resistencia antimicrobiana no ha desempeñado un papel relevante porque no se han encontrado cepas resistentes in vivo al tratamiento. A pesar de ello, la azitromicina sigue siendo un fármaco de primera elección ya que puede administrarse como una dosis única, lo que favorece el apego terapéutico.

Comprehensive Analysis of Germline Variants in Mexican Patients with Hereditary Breast and Ovarian Cancer Susceptibility.

Hereditary breast and ovarian cancer syndrome (HBOC) represents 5⁻10% of all patients with breast cancer and is associated with high-risk pathogenic alleles in BRCA1/2 genes, but only for 25% of cases. We aimed to find new pathogenic alleles in a panel of 143 cancer-predisposing genes in 300 Mexican cancer patients with suspicion of HBOC and 27 high-risk patients with a severe family history of cancer, using massive parallel sequencing. We found pathogenic variants in 23 genes, including BRCA1/2. In the group of cancer patients 15% (46/300) had a pathogenic variant; 11% (33/300) harbored variants with unknown clinical significance (VUS) and 74% (221/300) were negative. The high-risk group had 22% (6/27) of patients with pathogenic variants, 4% (1/27) had VUS and 74% (20/27) were negative. The most recurrent mutations were the Mexican founder deletion of exons 9-12 and the variant p.G228fs in BRCA1, each found in 5 of 17 patients with alterations in this gene. Rare VUS with potential impact at the protein level were found in 21 genes. Our results show for the first time in the Mexican population a higher contribution of pathogenic alleles in other susceptibility cancer genes (54%) than in BRCA1/2 (46%), highlighting the high locus heterogeneity of HBOC and the necessity of expanding genetic tests for this disease to include broader gene panels.

Association Between the SNP rs143383 + 104T/C in the GDF5 Gene and the Risk of Knee Osteoarthritis in a Population from Northern Mexico-A Case-Control Study.

BACKGROUND: Previous studies have found an association between the SNP rs143383 + 104T/C in the growth differentiation factor 5 (GDF5) gene and the risk of developing knee osteoarthritis (KOA) in various populations worldwide. OBJECTIVE: To discover if there is an association between the SNP rs143383 + 104T/C, in the GDF5 gene and the risk of developing KOA in individuals from northern Mexico. METHODS: We used a case-control study format that included 145 patients with KOA and 145 healthy controls unrelated to patients. A peripheral blood sample was taken for each of them to identify the SNP by means of real-time PCR according to standard protocols. RESULTS: We found a strong association between the TT genotype and the risk of developing KOA (OR = 1.7, 95% CI = 1.12-2.8, p = 0.014), but not in the heterozygous TC state (OR = 1.56, CI 95% = 0.58-4.17, p = 0.367). CONCLUSION: The TT genotype of the SNP rs143383 increases the susceptibility to KOA in the population of northern Mexico, according to the recessive segregation model.

Toxic Effect of Cadmium, Lead, and Arsenic on the Sertoli Cell: Mechanisms of Damage Involved.

Over the past decades, an increase has been described in exposure to environmental toxins; consequently, a series of studies has been carried out with the aim of identifying problems associated with health. One of the main risk factors is exposure to heavy metals. The adverse effects that these compounds exert on health are quite complex and difficult to elucidate, in that they act at different levels and there are various signaling pathways that are implicated in the mechanisms of damage. The Sertoli cells plays a role of vital importance during the process of spermatogenesis, and it has been identified as one of the principal targets of heavy metals. In the present review, cadmium, lead, and arsenic are broached as altering the physiology of the Sertoli cells, citing mechanisms that have been cited in the literature.

In Vitro Evaluation of Damage by Heavy Metals in Tight and Gap Junctions of Sertoli Cells.

The Sertoli cell plays a vital role during the spermatogenesis process and has been identified as one of the main targets of the toxic action of heavy metals on the seminiferous epithelium. In the present work, the effect of lead (Pb), Arsenic (As), and Cadmium (Cd) in primary cultures of Sertoli cells was analyzed by measuring the expression of the genes Cldn11, Ocln, and Gja1 that participate in the tight and gap junctions, which are responsible for maintaining the blood-testis barrier. Sertoli cells were isolated from the testes of Wistar rats. Sertoli cell cultures were exposed separately and at the same concentrations of three heavy metals for 48 h. Subsequently, gene expression was measured by real-time polymerase chain reaction. In the morphological analysis of the cultures, after 24 h, the cultures exposed to Cd showed greatest detachment of the monolayer, followed by those exposed to As and Pb. As for gene expression patterns, As induced a decrease in the expression of the Cldn11 gene at 24 and 48 h (p < 0.01) and in that of Ocln at 24 (p < 0.001) and 48 h (p < 0.01), whereas Cd induced overexpression of the Gja1 gene from day 1 of exposure (p < 0.001) and subexpression of the Ocln gene (p < 0.05) at 24 h. Because each of these three metals generated different expression patterns in the three genes, we can postulate that the mechanisms of damage that they induce are different; therefore, the effect that they exert on the Sertoli cell occurs through different pathways, generating changes in structural proteins, altering Sertoli cell morphology, and compromising its function in the regulation of the spermatogenesis process.

ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in Mexican women with familial and/or early-onset breast cancer.

OBJECTIVE: To assess whether in Mexican population the frequencies of ATM polymorphisms IVS24-9delT, IVS38-8-T>C, and 5557G>A in breast cancer (BC) cases and healthy controls were different from those found in other countries. MATERIALS AND METHODS: Frequencies of polymorphisms conferring BC risk IVS24-9delT, IVS38-8T>C, and 5557G>A were analyzed by PCR-RFLP in 94 patients with familial and/or early onset BC, and 97 healthy controls randomly selected. Allele frequencies analysis was done using χ(2) and Hardy-Weinberg test. RESULTS: Frequencies of heterozygous were: for 5557G>A, 13% cases, 0%controls (p=0.0009); for IVS24-9delT, 21% cases, 8% controls (p=0.0122); for IVS38-8T>C, only one case. 5557G>A and IVS24-9delT were more frequent in cases than in controls. The allelic frequencies found in 5557G>A are similar to those described by González-Hormazábal in Chile. CONCLUSION: The similarity of results in this polymorphism between Chilean and Mexican populations may be due to both being crossbred with an Amerindian-Spanish component, while differences may be due to fact that Chilean population has a greater European component than Mexican's.

ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in Mexican women with familial and/or early-onset breast cancer / Polimorfismos IVS24-9delT, IVS38-8T>C y 5557G>A en el gen ATM en mujeres mexicanas con cáncer de mama familiar o de inicio temprano

Objective. To assess whether in Mexican population the frequencies of ATM polymorphisms IVS24-9delT, IVS38-8-T>C, and 5557G>A in breast cancer (BC) cases and healthy controls were different from those found in other countries. Materials and methods. Frequencies of polymorphisms conferring BC risk IVS24-9delT, IVS38-8T>C, and 5557G>A were analyzed by PCR-RFLP in 94 patients with familial and/or early onset BC, and 97 healthy controls randomly selected. Allele frequencies analysis was done using χ² and Hardy-Weinberg test. Results. Frequencies of heterozygous were: for 5557G>A, 13% cases, 0%controls (p=0.0009); for IVS24-9delT, 21% cases, 8% controls (p=0.0122); for IVS38-8T>C, only one case. 5557G>A and IVS24-9delT were more frequent in cases than in controls. The allelic frequencies found in 5557G>A are similar to those described by González-Hormazábal in Chile. Conclusion. The similarity of results in this polymorphism between Chilean and Mexican populations may be due to both being crossbred with an Amerindian-Spanish component, while differences may be due to fact that Chilean population has a greater European component than Mexican's.

Objetivo. Evaluar si en la población mexicana las frecuencias de los polimorfismos IVS-9delT, IVS38-8T>C y 5557G>A en casos de cáncer de mama y en controles sanos son diferentes de las encontradas en otros países. Material y métodos. Los polimorfismos IVS24-9delT, IVS38-8T>C y 5557G>A fueron analizados mediante PCR-RFLPs en 94 pacientes con CM de tipo familiar o de inicio temprano y 97 testigos seleccionadas de forma aleatoria. El análisis de la frecuencia alélica se hizo mediante χ² y equilibrio de Hardy-Weinberg. Resultados. Las frecuencias de heterocigotos fueron 5557G>A, 13% de casos, 0% de testigos (p=0.0009); IVS24-9delT, 21% de casos, 8% de testigos (p=0.0l22); IVS38-8T>C, sólo un caso. 5557G>A y IVS24-9delT fueron más frecuentes en casos que en testigos. Las frecuencias alélicas encontradas en 5557G>A son similares a las descritas por González-Hormazábal en Chile. Conclusión. La similitud de resultados en este polimorfismo entre la población chilena y mexicana puede ser debida a que ambas son mestizas con un componente amerindio-español. Las diferencias encontradas podrían explicarse porque la población chilena tiene mayor componente europeo que la mexicana.

El extracto acuoso de ruta graveolens del norte de méxico causa apoptosis y muestra efecto antiproliferativo sobre el hígado de rata wistar: evidencia morfológica / Aqueous extract of ruta graveolens from the north of mexico causes apoptosis and shows antiproliferative effect on the liver of wistar rat: morphological evidence

Ruta graveolens es una planta nativa del Mediterráneo Oriental y del área Sur Occidental de Asia, de esta planta se han aislado más de 120 compuestos químicos. En un estudio previo en nuestro laboratorio se observó que un extracto acuoso de R. graveolens causó necrosis y alteraciones morfológicas sugestivas de apoptosis sobre el hígado de rata Wistar. El objetivo del presente estudio, fue evaluar la inducción de apoptosis y el posible efecto antiproliferativo in vivo de un extracto acuso de R. graveolens del norte de México, mediante métodos inmunohistoquímicos. Se utilizaron 25 ratas Wistar y se dividieron en 5 grupos (n=5). El grupo 1 correspondió al grupo control negativo, el grupo 2 o control positivo se trató con 100 mg de dexametasona/kg/día. Los grupos 3 y 4 se trataron con 30 y 100 mg de extracto de R. graveolens/kg/día respectivamente. Al grupo 5 se le administraron 100 mg de dexametasona/kg/día combinados con 100 mg de extracto de R. graveolens/kg/día. Las administraciones se realizaron vía intraperitoneal por tres días. Los animales se sacrificaron por dislocación cervical, y se tomaron muestras de hígado que se fijaron en formalina, posteriormente se incluyeron en bloques de parafina. Se obtuvieron cortes histológicos que se tiñeron con el método tricrómico de Masson. También se realizaron pruebas inmunohistoquímicas de TUNEL, anti-bcl-2 y anti-PCNA; además de un estudio morfométrico. Los resultados demuestran por primera vez el potencial apoptósico y antiproliferativo del extracto acuoso de R. graveolens del norte de México, sobre el hígado de rata Wistar. Se sugiere la posibilidad de emplear dosis menores a las administradas en este estudio del extracto acuoso de R. graveolens, para investigar su potencial uso como agente antineoplásico en estudios in vitro con líneas celulares tumorales e/o implantadas en modelos murinos de cáncer.

Ruta graveolens, is a native plant of the Eastern Mediterranean and the South Western area of Asia. From this plant, more than 120 chemical compounds have been isolated. In a previous study in our laboratory, we observed that an aqueous extract of R. graveolens, caused necrosis and morphological alterations suggestive of apoptosis on the liver of Wistar rats. The objective of this study, was to evaluate the induction of apoptosis and a possible antiproliferative effect in vivo of an aqueous extract of R. graveolens from the north of Mexico, by immunohistochemical methods. 25 Wistar rats were used and divided into 5 groups (n= 5). Group 1 corresponded to negative control group, group 2 or positive control was treated with 100 mg of dexamethasone/kg/day. Groups 3 and 4 were treated with 30 and 100 mg of extract of R. graveolens/kg/day respectively. Group 5 received the administration of 100 mg of dexamethasone/kg/day combined with 100 mg of extract of R. graveolens/kg/day. The administrations were by intraperitoneal via for three days. The animals were sacrificed by cervical dislocation, liver samples were taken, fixed in formalin and then samples were embedded in paraffin blocks. Histological sections were obtained and stained with Masson trichrome method. Immunohistochemical assays of TUNEL, anti-bcl-2, and anti-PCNA were performed. Also a morphometric study was carried out. Results show for the first time the potential apoptotic and antiproliferative effect of an aqueous extract of R. graveolens from the north of Mexico on the liver of Wistar rats. This suggests the use of lower doses of the extract of R. graveolens, to investigate its potential use as an antineoplastic agent, in studies in vitro with tumor cell lines and/or implanted in murine models of cancer.