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.
Abstract 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.
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.
The most common causes of congenital neutropenia are mutations in the
(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
, 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.
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.
To evaluate the role of the HLA-G rs66554220 variant in NS-V and its clinical features in Northwestern Mexicans.
We genotyped the rs66554220 variant by SSP-PCR in 197 NS-V patients and 198 age-sex matched non-related healthy individuals (HI).
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.
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.
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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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.
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.
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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