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BACKGROUND: Several guidelines recommend the use of different classifiers to determine the risk of recurrence (ROR) and treatment decisions in patients with HR+HER2- breast cancer. However, data are still lacking for their usefulness in Latin American (LA) patients. Our aim was to evaluate the comparative prognostic and predictive performance of different ROR classifiers in a real-world LA cohort. METHODS: The Molecular Profile of Breast Cancer Study (MPBCS) is an LA case-cohort study with 5-year follow-up. Stages I and II, clinically node-negative HR+HER2- patients (nâ =â 340) who received adjuvant hormone therapy and/or chemotherapy, were analyzed. Time-dependent receiver-operator characteristic-area under the curve, univariate and multivariate Cox proportional hazards regression (CPHR) models were used to compare the prognostic performance of several risk biomarkers. Multivariate CPHR with interaction models tested the predictive ability of selected risk classifiers. RESULTS: Within this cohort, transcriptomic-based classifiers such as the recurrence score (RS), EndoPredict (EP risk and EPClin), and PAM50-risk of recurrence scores (ROR-S and ROR-PC) presented better prognostic performances for node-negative patients (univariate C-index 0.61-0.68, adjusted C-index 0.77-0.80, adjusted hazard ratios [HR] between high and low risk: 4.06-9.97) than the traditional classifiers Ki67 and Nottingham Prognostic Index (univariate C-index 0.53-0.59, adjusted C-index 0.72-0.75, and adjusted HR 1.85-2.54). RS (and to some extent, EndoPredict) also showed predictive capacity for chemotherapy benefit in node-negative patients (interaction Pâ =â .0200 and .0510, respectively). CONCLUSION: In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort.
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HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator regions like 3'UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of endogen cell factors; nevertheless, the reports are discrepant and controversial. Herein, the relationship of the 14-bp Ins/Del variant (rs66554220) with breast cancer (BC) and its clinical characteristics were analyzed in 182 women with non-familial BC and 221 disease-free women as a reference group. Both groups from western Mexico and sex-age-matched (sm-RG). The rs66554220 variant was amplified by SSP-PCR and the fragments were visualized in polyacrylamide gel electrophoresis. The variant rs66554220 was not associated with BC in our population. However, we suggest the Ins allele as a possible risk factor for developing BC at clinical stage IV (OR = 3.05, 95% CI = 1.16-7.96, p = 0.01); nevertheless, given the small stratified sample size (n = 11, statistical power = 41%), this is inconclusive. In conclusion, the 14-bp Ins/Del (rs66554220) variant of HLA-G is not associated with BC in the Mexican population, but might be related to advanced breast tumors. Further studies are required.
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Introduction: The HLA-G molecule functions as a critical immunomodulatory checkpoint, its expression is significantly associated with pathological processes that may be responsible in part for autoimmune conditions such as non-segmental vitiligo (NS-V), characterized by chronic skin depigmentation. In this sense, the rs66554220 (14 bp ID) variant located in the 3'UTR, implicated in the regulation of HLA-G production, is associated with autoimmune diseases. Aim: To evaluate the role of the HLA-G rs66554220 variant in NS-V and its clinical features in Northwestern Mexicans. Material and methods: We genotyped the rs66554220 variant by SSP-PCR in 197 NS-V patients and 198 age-sex matched non-related healthy individuals (HI). Results: Del allele and genotype Del/Ins were the most prevalent in both study groups (NS-V/HI = 56%/55% and 46.70%/46.46%, respectively). Despite lacking association between the variant and NS-V, we found an association of the Ins allele in different inheritance models with familial clustering, onset of the illness, universal clinical subtype and Koebner's phenomenon. Conclusions: The rs66554220 (14 bp ID) variant is not a risk factor for NS-V in the Mexican population studied. To our knowledge, this is the first report about the topic in the Mexican population and worldwide that includes clinical features related with this HLA-G genetic variant.
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BACKGROUND: Functional variants -173 G > C (rs755622) and -794CATT5-8 (rs5844572) MIF gene have been associated with the risk in several types of cancer, as well as with the increase of soluble levels of MIF and TNFα. However, in previous studies contradictory and uncertain results have been presented on the implication of MIF polymorphisms with the association in cancer, specifically in breast cancer (BC). We investigated whether the variants are associated with the susceptibility to develop BC and the soluble levels of MIF and TNFα in women with BC from western Mexico. MATERIALS AND METHODS: A total of 152 women with BC and 182 control subjects (CS) were enrolled in this study. The determination of genotypes -173 G > C and -794 CATT5-8 MIF polymorphisms was performed by PCR-RFLP and PCR, respectively. In addition, the soluble levels of MIF and TNFα in both studied groups were quantified by ELISA and MILLIPLEX assay, respectively. RESULTS: The most frequent allele found in BC was the G (74.3%) and 6 (54%) in the variants -173G > C and -794 CATT5-8 , respectively, without significant differences in both groups. Nevertheless, the women with BC carriers -173*C and -794CATT7 have higher levels of MIF in comparison with CS. An increase of MIF (BC: 11.1 ng/mL vs CS: 5.2 ng/mL, P < .001) and TNFα (BC: 24.9 ng/mL vs CS: 9.9 pg/mL, P < .001) was found. CONCLUSION: The functional variants of MIF are not genetic susceptibility markers for BC. Nevertheless, the alleles -173*C and -794CATT7 are associated with the increase of MIF circulating in women with BC.
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Neoplasias de la Mama/genética , Oxidorreductasas Intramoleculares/sangre , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/sangre , Factores Inhibidores de la Migración de Macrófagos/genética , Factor de Necrosis Tumoral alfa/sangre , Adulto , Neoplasias de la Mama/sangre , Estudios de Casos y Controles , Estudios Transversales , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , México , Persona de Mediana Edad , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Solubilidad , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
INTRODUCTION: Common variable immunodeficiency (CVID) is the main symptomatic primary immunodeficiency and is associated with complex immune disorders. Gut microbiota interacts closely with the immune system, and intestinal dysbiosis is related to multiple diseases. OBJECTIVE: To describe for the first time the composition of gut microbiota in Mexican patients with CVID. METHODS: Fecal samples from five patients with CVID were collected and massive sequencing of the V3-V4 region of 16S rRNA gene was carried out using illumina technology. RESULTS: Bacterial relative abundance was observed at all taxonomic levels. Firmicutes, Actinobacteria and Verrucomicrobia were the predominant phyla. The Clostridia class and the Clostridial order were the most common in their respective taxon; the Ruminococcaceae family predominated. A total of 166 genera were reported, with the most abundant being Faecalibacterium. Five species were identified, but only Bifidobacterium longum was present in all patients. CONCLUSIONS: Unlike healthy subjects' gut microbiota, where Firmicutes and Bacteroidetes predominate, the microbiota of the patients with CVID considered in this study was abundant in Firmicutes, Actinobacteria and Verrucomicrobia. The low presence of Bacteroidetes and high abundance of Firmicutes might indicate the existence of intestinal dysbiosis in these patients.
INTRODUCCIÓN: La inmunodeficiencia común variable (IDCV) es la principal inmunodeficiencia primaria sintomática y cursa con alteraciones inmunes complejas. La microbiota intestinal interactúa estrechamente con el sistema inmune y la disbiosis intestinal está relacionada con múltiples patologías. OBJETIVO: Describir por primera vez la composición de la microbiota intestinal en pacientes mexicanos con inmunodeficiencia común variable. MÉTODO: Se recolectaron muestras fecales de cinco pacientes con inmunodeficiencia común variable y se llevó a cabo secuenciación masiva de la región V3-V4 del gen 16S rRNA mediante tecnología Illumina. RESULTADOS: Se observó abundancia bacteriana relativa a todos los niveles taxonómicos. Firmicutes, Actinobacteria y Verrucomicrobia fueron los filos predominantes. La clase Clostridia y el orden Clostridiales fueron los principales en su respectivo taxón; predominó la familia Ruminococcaceae. Se reportaron 166 géneros, el más abundante fue Faecalibacterium. Se identificaron cinco especies, pero solo Bifidobacterium longum estuvo presente en todos los pacientes. CONCLUSIONES: A diferencia de la microbiota intestinal de sujetos sanos en quienes predominan Firmicutes y Bacteroidetes, en los pacientes con inmunodeficiencia común variable considerados en este estudio fueron abundantes Firmicutes, Actinobacterias y Verrucomicrobia. La baja abundancia de bacteroidetes y alta de firmicutes podrían significar disbiosis intestinal.
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Inmunodeficiencia Variable Común/microbiología , Disbiosis/microbiología , Microbioma Gastrointestinal , Actinobacteria/aislamiento & purificación , Bacterias/clasificación , Bacteroidetes/aislamiento & purificación , Heces/microbiología , Firmicutes/aislamiento & purificación , Humanos , México , ARN Ribosómico 16S/genética , Verrucomicrobia/aislamiento & purificaciónRESUMEN
INTRODUCTION: Common variable immunodeficiency (CVID) is the main symptomatic primary immunodeficiency and is associated with complex immune disorders. Gut microbiota interacts closely with the immune system, and intestinal dysbiosis is related to multiple diseases. OBJECTIVE: To describe for the first time the composition of gut microbiota in Mexican patients with CVID. METHODS: Fecal samples from five patients with CVID were collected and massive sequencing of the V3-V4 region of 16S rRNA gene was carried out using illumina technology. RESULTS: Bacterial relative abundance was observed at all taxonomic levels. Firmicutes, Actinobacteria and Verrucomicrobia were the predominant phyla. The Clostridia class and the Clostridial order were the most common in their respective taxon; the Ruminococcaceae family predominated. A total of 166 genera were reported, with the most abundant being Faecalibacterium. Five species were identified, but only Bifidobacterium longum was present in all patients. CONCLUSIONS: Unlike healthy subjects' gut microbiota, where Firmicutes and Bacteroidetes predominate, the microbiota of the patients with CVID considered in this study was abundant in Firmicutes, Actinobacteria and Verrucomicrobia. The low presence of Bacteroidetes and high abundance of Firmicutes might indicate the existence of intestinal dysbiosis in these patients.
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Inmunodeficiencia Variable Común/microbiología , Microbioma Gastrointestinal , Actinobacteria/aislamiento & purificación , Adulto , Bacterias/clasificación , Bacteroidetes/aislamiento & purificación , Bifidobacterium longum/aislamiento & purificación , Clostridiales/aislamiento & purificación , Clostridium/aislamiento & purificación , Disbiosis/inmunología , Disbiosis/microbiología , Faecalibacterium/aislamiento & purificación , Heces/microbiología , Firmicutes/aislamiento & purificación , Microbioma Gastrointestinal/inmunología , Humanos , México , ARN Ribosómico 16S/genética , Ruminococcus/aislamiento & purificación , Verrucomicrobia/aislamiento & purificaciónRESUMEN
Interleukin-10 (IL-10) is an immunomodulatory cytokine that plays a pivotal role in the pathogenesis of acute coronary syndromes (ACS). Here, we evaluated the role of IL10 promoter variants as markers for ACS susceptibility in Western Mexican patients as well as its association with IL10 mRNA and IL-10 plasma levels. Three promoter variants (- 1082 A > G, - 819 T > C and - 592 A > C) were analyzed in 300 ACS patients and 300 control group (CG) individuals. IL10 relative gene expression was evaluated in peripheral blood mononuclear cells (PBMC) and IL-10 levels were quantified in plasma. The allelic, genotypic and haplotypic frequencies did not show significant differences between groups. ACS patients had sevenfold higher mRNA IL10 level compared to CG (p = 0.0013). Homozygous C/C carriers in both - 819 T > C and - 592 A > C variants had 0.4-fold higher IL10 mRNA expression than heterozygous and polymorphic allele homozygous genotypes (p = 0.0357) in ACS group. There were significant differences in plasma IL-10 levels in CG and ACS group (1.001 vs 1.777 pg/mL, p = 0.0051). The variants were not markers of susceptibility to ACS in Western Mexican individuals. ACS patients showed higher IL10 expression than CG individuals which could be mediated by - 819 T > C and - 592 A > C variants and pharmacotherapy.
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Síndrome Coronario Agudo , Predisposición Genética a la Enfermedad , Interleucina-10 , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Humanos , Interleucina-10/genética , Interleucina-10/sangre , Síndrome Coronario Agudo/genética , Síndrome Coronario Agudo/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios de Casos y Controles , Genotipo , Alelos , Biomarcadores/sangre , México , Leucocitos Mononucleares/metabolismo , Frecuencia de los Genes , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
INTRODUCTION: The expression of plasminogen activator inhibitor type 1 (PAI-1), vascular endothelial growth factor (VEGF), and transforming growth factor ß1 (TGF-ß1) participates in the angiogenesis of several cancer types. The goal of this study was to investigate polymorphisms in genes related to angiogenesis (PAI-1-675 4G/5G, VEGF C936T, and TGF-ß1 G-800A) to evaluate the risk for developing uterine cervical cancer (UCC). METHODS: In a case-control study, 100 healthy subjects and 100 patients with UCC from Mexico were included. We determined the genetic profile of the polymorphic markers, which were evaluated by polymerase chain reaction using a sequence-specific primer. RESULTS: There was no statistical difference in the allele distribution from the intergroup comparisons of PAI-1 675 4G/5G and VEGF C936T data; however, a significant difference was observed within TGF-ß1 G-800A. The linkage disequilibrium analysis revealed that PAI-1 -675 4G and TGF-ß1 -800A pair-haplotype was in strong linkage disequilibrium with a significantly increased risk (odds ratio, 3.44; 95% confidence interval, 1.66-7.25) to UCC. CONCLUSIONS: The polymorphisms in the genes related to angiogenesis -675 4G/5G PAI-1 and G-800A TGF-ß1, segregated solely or combined, might contribute to the increased susceptibility to UCC in a Mexican population.
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Biomarcadores de Tumor/genética , Neovascularización Patológica/genética , Inhibidor 1 de Activador Plasminogénico/genética , Polimorfismo de Nucleótido Simple/genética , Factor de Crecimiento Transformador beta1/genética , Neoplasias del Cuello Uterino/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adolescente , Adulto , Estudios de Casos y Controles , Cuello del Útero/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos/genética , Humanos , Desequilibrio de Ligamiento , México/epidemiología , Reacción en Cadena de la Polimerasa , Pronóstico , Neoplasias del Cuello Uterino/epidemiología , Adulto JovenRESUMEN
Breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer and, in terms of mortality, is the fifth leading cause with 684,996 new deaths (6.7% of all cancer-related deaths) and the highest mortality amongst all cancers (15.5%) in women. Selective estrogen-receptor modulators (SERMs) have been used for the last thirty years for estrogen receptor-positive (ER+) BC prevention and treatment. Tamoxifen (TAM), the most widely used SERM, is orally administered and its long-term oral administration has been associated to toxicity and adverse side effects. Endoxifen (EDX) is one of the known active metabolites of TAM, with an affinity to ERα 100 times higher than TAM. Furthermore, EDX has shown antiproliferative activity against the ER+ BC cell line MCF-7. Alternative administration routes that avoid the metabolic processing of TAM seem an appealing alternative to its oral administration. With this aim, we have prepared a polymeric gel-like solution of Pluronic® F127 as vehicle for topical administration of EDX. In order to shed light on the potential clinical use of this formulation, we have compared it with the standard pharmaceutical form, i.e. orally administered TAM. The biodistribution, antitumor efficacy and toxic effects of topical EDX and oral TAM were evaluated in ER+ tumor xenograft athymic nu/nu mouse models. The results showed a statistically significant antitumor effect and reduced toxicity of topical EDX as compared to oral TAM or empty F127 gel. This novel administration route of SERMs could also have a strong impact in the prevention of BC at early development stages and could help to ameliorate the mortality and morbidity related to this disease.
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Neoplasias de la Mama , Moduladores Selectivos de los Receptores de Estrógeno , Humanos , Femenino , Ratones , Animales , Receptores de Estrógenos/metabolismo , Modelos Animales de Enfermedad , Distribución Tisular , Tamoxifeno/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismoRESUMEN
The most common causes of congenital neutropenia are mutations in the ELANE (Elastase, Neutrophil Expressed) gene (19p13.3), mostly in exon 5 and the distal portion of exon 4, which result in different clinical phenotypes of neutropenia. Here, we report two pathogenic mutations in ELANE, namely, c.607G>C (p.Gly203Arg) and a novel variant c.416C>G (p.Pro139Arg), found in two Mexican families ascertained via patients with congenital neutropenia who responded positively to the granulocyte colony-stimulating factor (G-CSF) treatment. These findings highlight the usefulness of identifying variants in patients with inborn errors of immunity for early clinical management and the need to rule out mosaicism in noncarrier parents with more than one case in the family.
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Neutropenia , Humanos , Síndromes Congénitos de Insuficiencia de la Médula Ósea/genética , Elastasa de Leucocito/genética , Mutación , Neutropenia/congénitoRESUMEN
Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).
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OBJECTIVE: To estimate the frequency of chronic urticaria in patients who attended an allergy service in a tertiary care hospital; in addition, the main clinical characteristics are described. METHODS: In a period of 7 months, a total of 96 patients who were over 18 years of age were analyzed; they had been diagnosed with chronic spontaneous urticaria and chronic inducible urticaria. RESULTS: The frequency of chronic urticaria was of 1.31 % (n=98); 53 % were associated with some allergic pathology, and 54 % showed an alteration in the paraclinical tests. Chronic spontaneous urticaria was found in 80 % of the patients; and in 62 % of them, the urticaria was associated with angioedema. Chronic urticaria was controlled in 19 % of the studied population with the use of a single antihistamine. CONCLUSIONS: The frequency of chronic urticaria in our study was lower than the frequency reported nationwide.
Objetivo: Estimar la frecuencia de la urticaria crónica en pacientes que acudieron a un servicio de alergología en un hospital de tercer nivel; complementariamente, se hace una descripción de las principales características clínicas. Métodos: Se analizaron un total de 96 pacientes con UC espontánea y UC inducible, con edad > 18 años, en un lapso de 7 meses. Resultados: La frecuencia de UC fue de 1.31 % (n = 98); 53 % se asociaron con alguna enfermedad alérgica y 54 % mostró algún tipo de alteración en los estudios paraclínicos. En 80 % de los pacientes, la urticaria fue crónica espontánea y en 62 % se vio asociada con angioedema. El 19 % de los casos obtuvo control de la UC con el uso de un solo antihistamínico. Conclusiones: La frecuencia de UC en nuestro estudio fue inferior con respecto a la informada a nivel nacional.
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Angioedema , Urticaria Crónica , Urticaria , Adolescente , Adulto , Angioedema/epidemiología , Enfermedad Crónica , Humanos , Centros de Atención Terciaria , Urticaria/epidemiologíaRESUMEN
The detection of premenopausal women at high risk of breast cancer is key to chemoprevention. Therapy with selective estrogen receptor modulators (SERMs) induces a significant antiproliferative effect in estrogen receptor (ER) positive breast cancer. This review was designed according the guidelines of the 2009 PRISMA statement. Searching different databases, including PubMed, MedlinePlus, PLoS One, Cochrane Breast Cancer Specialized Register, Clinical Trials.gov and American Society of Clinical Oncology. From 168 records screened, 15 full text articles were assessed for eligibility and only 7 studies met the inclusion criteria. Three of the studies included analyzed changes in Ki-67 expression, revealing weaker expression after treatment with acolbifene and raloxifene (P<0.001). Three studies also analyzed the breast volume by magnetic resonance imagining (MRI) and demonstrate a significant difference after 1 year with raloxifene treatment (P=0.0017). Moreover, a 20% reduction in breast density was observed after a 2-year treatment with tamoxifen in premenopausal women. SERMs reduce the risk of developing breast cancer. The studies reviewed here demonstrate the modulation of Ki-67 expression and changes in breast density, suggesting an important preventive role for this group of drugs in prevention for premenopausal women at high risk of developing breast cancer.
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Introduction: Interleukin-6 (IL-6) is a circulating proinflammatory cytokine that fulfills an important role in the survival and proliferation of cancer cells. Overexpression of IL-6, possibly due to the -174G>C and -596G>A polymorphisms in the IL6 gene, has been shown to be related to breast cancer (BC) and a more aggressive course of the disease. Aim: To determine the influence of the -174G>C and -596G>A polymorphisms of the IL6 gene on the circulating levels of IL-6 in BC patients from Jalisco, México. Methodology: Genotyping of the two polymorphisms was carried out on 208 BC patients and 219 healthy controls through polymerase chain reaction-restriction fragment length polymorphism analyses. In addition, the plasma IL-6 concentration levels were measured in the BC patients. Results: There was no significant association between BC and the IL-6 alleles and genotypes (-174G>C, p = 0.276; -596G>A, p = 0.762) under study. Similarly, there were no significant differences in the mean plasma IL-6 concentrations associated with the polymorphisms that were analyzed (-174G>C, p = 0.839; -596G>A, p = 0.848). Conclusions: No evidence was found that the analyzed polymorphisms are associated with the IL-6 expression or concentration in patients suffering from BC from Jalisco, Mexico.
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Neoplasias de la Mama/genética , Interleucina-6/genética , Adulto , Neoplasias de la Mama/sangre , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Interleucina-6/sangre , México/epidemiología , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Regiones Promotoras GenéticasRESUMEN
Ovarian cancer (OC) is the deadliest gynecological cancer. Standard treatment of OC is based on cytoreductive surgery followed by chemotherapy with platinum drugs and taxanes; however, innate and acquired drug-resistance is frequently observed followed by a relapse after treatment, thus, more efficient therapeutic approaches are required. Combination therapies involving phototherapies and chemotherapy (the so-called chemophototherapy) may have enhanced efficacy against cancer, by attacking cancer cells through different mechanisms, including DNA-damage and thermally driven cell membrane and cytoskeleton damage. We have designed and synthesized poly(lactic-co-glycolic) nanoparticles (PLGA NPs) containing the chemo-drug carboplatin (CP), and the near infrared (NIR) photosensitizer indocyanine green (ICG). We have evaluated the drug release profile, the photodynamic ROS generation and photothermal capacities of the NPs. Also, the antitumoral efficiency of the NPs was evaluated using the SKOV-3 cell line as an in vitro OC model, observing an enhanced cytotoxic effect when irradiating cells with an 800â¯nm laser. Evidence here shown supports the potential application of the biodegradable photoresponsive NPs in the clinical stage due to the biocompatibility of the materials used, the spatiotemporal control of the therapy and, also, the less likely development of resistance against the combinatorial therapy.
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Hipertermia Inducida , Nanopartículas , Neoplasias Ováricas , Fotoquimioterapia , Animales , Línea Celular Tumoral , Femenino , Humanos , Verde de Indocianina , Ratones , Ratones Desnudos , Neoplasias Ováricas/tratamiento farmacológico , FototerapiaRESUMEN
INTRODUCTION: Short tandem repeats (STRs) are the DNA polymorphisms most widely used in forensic genetics and parentage testing. Most common series of STRs are those from FBI (CODIS) and from INTERPOL. While there are data related to the first group, no studies are still known in Mexican populations in regard of the INTERPOL set. OBJECTIVE: To describe the genetic characteristics of five INTERPOL STRs and to estimate their main forensic parameters in a population from western Mexico. MATERIAL AND METHODS: Samples from 100 random volunteers from the State of Jalisco were PCR typed for STRs F13B, D2S1338, FESFPS, Penta D and Penta E. RESULTS: Genotype proportions in all five STRs were in agreement with Hardy-Weinberg expectations (p > 0.05). Heterocygosity varied from 0.68 for FESFPS to 0.91 for Penta E markers. Power of discrimination (PD) and exclusion probability (EP) were in the 0.83-0.97 and 0.46-0.75 ranges, respectively. The five combined STRs give a PE > 0.99143 and PD > 0.99999. CONCLUSIONS: These results contribute to establish data bases representative of western Mexico and are useful in DNA forensic and parentage studies.
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Población Negra/genética , Etnicidad/genética , Genética Forense/métodos , Indígenas Norteamericanos/genética , Repeticiones de Microsatélite , Población Blanca/genética , Adolescente , Adulto , Anciano , Alelos , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Genotipo , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Muestreo , España/etnología , Adulto JovenRESUMEN
Breast cancer (BC) is a health problem worldwide; there is evidence that inflammatory cytokines are increased in BC. Macrophage migration inhibitory factor (MIF) has multiple effects on immune cells, inflammation and cancer. Besides, in previous studies, contradictory and uncertain results have been presented on the implication of Th17 cytokine profile in BC. The aim of this study was to evaluate the plasma levels of MIF and the Th17 cytokine profile in BC and their association with their molecular subtypes and clinical stage. A total of 150 women with BC of Ella Binational Breast Cancer Study and 60 healthy women (HW) were evaluated in cross-sectional study. The molecular subtypes were identified by immunohistochemistry. The plasma levels of MIF were quantified by ELISA and Th17 cytokine profile by multiplex system. MIF and IL-17 were significantly increased in BC versus HW (11.1 vs. 5.2 ng/mL and 14.8 pg/mL vs. 2.5 pg/mL p < 0.001, respectively). Our analysis showed that both MIF and IL-17A were associated with increased risk of breast cancer (OR 3.85 CI 95% 1.98-7.50 and OR 4.51 95% 1.83-11.15, respectively), higher in aggressive subtypes Luminal B, HER2 and TN. Likewise, we observed positive correlation between MIF and IL-17A (p < 0.001). In addition, IL-17E was lower in BC versus HW (p <0.001). Likewise, we observed a positive correlation between MIF and IL-17A (p < 0.001). In conclusion, both MIF and IL-17A were associated with high risk for breast cancer and aggressive molecular subtypes.
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Neoplasias de la Mama/patología , Citocinas/sangre , Oxidorreductasas Intramoleculares/sangre , Factores Inhibidores de la Migración de Macrófagos/sangre , Células Th17/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana EdadRESUMEN
INTRODUCTION: Premature rupture of membranes (PRM) is a late pregnancy complication commonly associated with preterm delivery (PD). Although several markers related to the renin-angiotensin system (RAS) have been evaluated in certain pregnancy complications, only the angiotensin-converting enzyme (ACE) I/D variant has been studied in PD-PRM. The aim of this survey was to investigate the association of the polymorphisms (angiotensin II type 1 [AT1] receptor T174M and M235T, renin G2805A, ACE I/D and AT1-receptor A1166C) of the genes of RAS in women with PD-PRM. DESIGN: Deoxyribonucleic acid samples from 89 Mexican Mestizo women with PD and PRM and 224-288 controls were studied. Polymorphisms were analysed by polymerase chain reaction-restricted fragment length polymorphism or sequence specific primer assays. RESULTS: For all loci, genotype distribution was in agreement with Hardy-Weinberg expectations in the control group. Significant intergroup difference (case vs. control) was seen for angiotensinogen (AGT) M235T polymorphism, with an increased allele M235 in affected cases (50% vs. 40% in controls). Analysis of two-locus haplotype agrees with an independent segregation of physically unlinked genes. Haplotype AGT 174T-235M was also increased (50% vs. 40% in controls). CONCLUSIONS: Physically unlinked genes involved in RAS segregate independently. The AGT 174-235 region is associated with PD-PRM in this population.
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Rotura Prematura de Membranas Fetales/genética , Polimorfismo Genético , Nacimiento Prematuro/genética , Sistema Renina-Angiotensina/genética , Adolescente , Adulto , Angiotensinógeno/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Haplotipos , Humanos , Desequilibrio de Ligamiento , EmbarazoRESUMEN
An association between thrombophilic genes and obstetric conditions with early pregnancy termination has been previously proposed. In the present study we attempted to evaluate the possible association between thrombophilic genetic polymorphisms and habitual abortion (HA). Samples from two groups of volunteers were analyzed. The experimental group (n>100) was conformed by women attending the Centro Medico de Occidente, IMSS and their male couples, with a reproductive history ofat least three miscarriages. The reference group (n > 200) was composed by male and female healthy adults living in the state of Jalisco, Mexico. DNA was extracted from peripheral blood, and polymorphisms FII G20210A , FVG1691A, MTHFR C677T, ECA IID y TNF G-308A were typed by PCR-RFLP or -SSP. Genotype proportions in the reference group were in agreement with the HardyWeinberg expectations. Allele, genotype, and phenotype proportion inter-group comparisons did not show statistically significant differences. The present results could not demonstrate that thrombophilic polymorphisms constitute risk factors for HA in Jalisco.
Asunto(s)
Aborto Habitual/genética , Polimorfismo Genético , Trombofilia/genética , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Embarazo , Factores de RiesgoRESUMEN
INTRODUCTION: Down syndrome (DS) or trisomy 21 is the most common chromosomal abnormality in live birth children. Most cases are regular trisomies 21 secondary to a maternal non-disjunction (ND). Meiotic and parental origins have been recently investigated by segregating genetic markers from DNA hypervariable regions. OBJECTIVE: To identify the meiotic and parental origin in children with regular trisomy 21. MATERIALS AND METHODS: There were analyze 20 groups of three (every group included parents and child with Down syndrome). There were used soothe following markers: D21S11, D21S1260, and D21S265. RESULTS: The ND occurred during the first meiotic division (M1) in 13 cases and at the second meiotic division (M2) in the other seven. Twelve out of the 13 NDs from the first group were maternal and one paternal. The parental origin within the M2 group was not elucidated. CONCLUSIONS: Meiotic origin was identified in all cases. As in other reports, the origin of trisomy 21 in the present population is mainly secondary to a maternal ND in M1.