Publications by authors named "Adrián Daneri-Navarro"

36 Publications

Microfluidics-assisted conjugation of chitosan-coated polymeric nanoparticles with antibodies: Significance in drug release, uptake, and cytotoxicity in breast cancer cells.

J Colloid Interface Sci 2021 Jun 13;591:440-450. Epub 2021 Feb 13.

Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico. Electronic address:

Nanoparticle-based drug delivery systems, in combination with high-affinity disease-specific targeting ligands, provide a sophisticated landscape in cancer theranostics. Due to their high diversity and specificity to target cells, antibodies are extensively used to provide bioactivity to a plethora of nanoparticulate systems. However, controlled and reproducible assembly of nanoparticles (NPs) with these targeting ligands remains a challenge. In this context, determinants such as ligand density and orientation, play a significant role in antibody bioactivity; nevertheless, these factors are complicated to control in traditional bulk labeling methods. Here, we propose a microfluidic-assisted methodology using a polydimethylsiloxane (PDMS) Y-shaped microreactor for the covalent conjugation of Trastuzumab (TZB), a recombinant antibody targeting HER2 (human epidermal growth factor receptor 2), to doxorubicin-loaded PLGA/Chitosan NPs (PLGA/DOX/Ch NPs) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (sNHS) mediated bioconjugation reactions. Our labeling approach led to smaller and less disperse nanoparticle-antibody conjugates providing differential performance when compared to bulk-labeled NPs in terms of drug release kinetics (fitted and analyzed with DDSolver), cell uptake/labeling, and cytotoxic activity on HER2 + breast cancer cells in vitro. By controlling NP-antibody interactions in a laminar regime, we managed to optimize NP labeling with antibodies resulting in ordered coronas with optimal orientation and density for bioactivity, providing a cheap and reproducible, one-step method for labeling NPs with globular targeting moieties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2021.02.031DOI Listing
June 2021

Biodegradable photoresponsive nanoparticles for chemo-, photothermal- and photodynamic therapy of ovarian cancer.

Mater Sci Eng C Mater Biol Appl 2020 Nov 17;116:111196. Epub 2020 Jun 17.

Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico. Electronic address:

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 800 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2020.111196DOI Listing
November 2020

The -174G>C and -596G>A Polymorphisms Are Not Associated with Circulating IL-6 Levels in Breast Cancer Patients from Jalisco, México.

Genet Test Mol Biomarkers 2020 Apr 26;24(4):224-228. Epub 2020 Mar 26.

Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

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 gene, has been shown to be related to breast cancer (BC) and a more aggressive course of the disease. To determine the influence of the -174G>C and -596G>A polymorphisms of the gene on the circulating levels of IL-6 in BC patients from Jalisco, México. 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. There was no significant association between BC and the alleles and genotypes (-174G>C,  = 0.276; -596G>A,  = 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,  = 0.839; -596G>A,  = 0.848). 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/gtmb.2019.0141DOI Listing
April 2020

Establishment of Murine Model of Kidney Failure Induced by Severe Ischemia-Reperfusion Injury Useful to Evaluate Transplantation and Regenerative Therapies.

Transplant Proc 2020 May 10;52(4):1202-1205. Epub 2020 Mar 10.

Laboratory of Tissue Engineering and Transplant, Department of Physiology, University Center for Health Sciences, University of Guadalajara, Jalisco, Mexico; cGMP Cell Processing Facility, University Center for Health Sciences, University of Guadalajara, Mexico. Electronic address:

Background: Severe ischemia-reperfusion injury (SIRI) seems to be the key factor that can significantly affect the function of both native kidneys and renal allografts. Therefore, the development of a successful strategy is of a paramount importance in both basic and clinical research.

Methods: To determine the effects of SIRI on the native kidney function, a murine model was planned as follows: group 1 (n = 6) mice underwent to nephrectomy plus ischemia-reperfusion injury for 30 minutes; group 2 (n = 6) mice underwent to nephrectomy without ischemia-reperfusion injury and thus served as sham controls for SIRI. The results of serum creatinine (SCr) were analyzed using Mann-Whitney U tests to calculate the significance between mean values. Survival between groups was measured by Kaplan-Meier test.

Results: To reliably achieve an elevation of SCr levels animals were exposed to a SIRI. The values of SCr increased from 0.35 (SD, 0.09) mg/dL to about 2-fold within 2 days and 3-fold within the following 5 days. Under these given conditions the mice displayed signs and histologic findings of severe kidney damage. The survival rate was about 83% of the animals within a week, and they showed no capacity of complete spontaneous self-regeneration.

Conclusions: In this study, we aim to establish a murine model with extensive structural kidney damage and significant elevation of SCr levels, which could be used in basic and translational research of transplantation and regenerative therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transproceed.2020.02.014DOI Listing
May 2020

Association of the genetic variants (-794 CATT5-8 and -173 G > C) of macrophage migration inhibitory factor (MIF) with higher soluble levels of MIF and TNFα in women with breast cancer.

J Clin Lab Anal 2020 May 24;34(5):e23209. Epub 2020 Jan 24.

Departamento de Biología Molecular y Genómica, Instituto de Investigación en Ciencias Biomédicas (IICB), Universidad de Guadalajara, Guadalajara, México.

Background: Functional variants -173 G > C (rs755622) and -794CATT (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 CATT 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 CATT , respectively, without significant differences in both groups. Nevertheless, the women with BC carriers -173*C and -794CATT 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 -794CATT are associated with the increase of MIF circulating in women with BC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.23209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246356PMC
May 2020

Circulating soluble levels of MIF in women with breast cancer in the molecular subtypes: relationship with Th17 cytokine profile.

Clin Exp Med 2019 Aug 18;19(3):385-391. Epub 2019 May 18.

Laboratorio de Inmunología, Departamento de Fisiología, CUCS, Universidad de Guadalajara, Sierra Mojada # 950, Colonia Independencia, CP 44340, Guadalajara, Jalisco, Mexico.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10238-019-00559-6DOI Listing
August 2019

Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy.

Colloids Surf B Biointerfaces 2019 Jun 6;178:199-207. Epub 2019 Mar 6.

Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, 44340, Mexico.

The conventional treatment (cytoreduction combined with cisplatin/carboplatin and taxane drugs) of ovarian cancer has a high rate of failure and recurrence despite a favorable initial response. This lack of success is usually attributed to the development of multidrug resistance mechanisms by cancer cells and avoidance of the anti-growth effects of monoclonal targeted therapeutic antibodies. The disease, like other cancers, is characterized by the overexpression of molecular markers, including HER2 receptors. Preclinical and clinical studies with trastuzumab, a HER2-targeted therapeutic antibody, reveal a low improvement of the outcomes of HER2 positive ovarian cancer patients. Therefore, here, we propose a cisplatin-loaded, HER2 targeted poly(lactic-co-glycolic) nanoplatform, a system capable to escape the drug-efflux effect and to take advantage of the overexpressed HER2 receptors, using them as docks for targeted chemotherapy. The NP/trastuzumab ratio was determined after fluorescein labeling of antibodies and quantification of fluorescence in NPs. The system was also characterized in terms of size, zeta potential, drug release kinetics, cytotoxicity and cellular internalization in the epithelial ovarian cancer cell line SKOV-3, and compared with the HER2 negative breast cancer cell line HCC70. Our results show an increased cytotoxicity of NPs as compared to free cisplatin, and moreover, an enhanced internalization and cytotoxicity due to the bionfunctionalization of NPs with the monoclonal antibody.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.colsurfb.2019.03.011DOI Listing
June 2019

Rational Surface Engineering of Colloidal Drug Delivery Systems for Biological Applications.

Curr Top Med Chem 2018 ;18(14):1224-1241

Department of Physiology, Laboratory of Immunology, Health Sciences Centre (CUCS) University of Guadalajara, Guadalajara, 44340, Mexico.

The use of colloidal particles as drug delivery carriers holds a great promise in terms of improvement of traditional treatment and diagnosis of human diseases. Nano- and microsized particles of a different composition including organic and inorganic materials can be fabricated with a great control over size, shape and surface properties. Nevertheless, only some few formulations have surpassed the benchtop and reached the bedside. The principal obstacle of colloidal drug delivery systems is their poor accumulation in target tissues, organs and cells, mainly by efficient sequestration and elimination by the mononuclear phagocytic system. Recent evidence suggests that, besides size, the surface character of colloidal systems is the most determinant design parameter that may ultimately guarantee successful biological performance. To approach these issues, materials designers and engineers can make use of multiple strategies and tools to finely modulate the particles' surface towards highly efficient and biocompatible materials. In this article, we provide an overview of the most relevant colloidal drug delivery systems, a summary of the available literature regarding the effects of surface charge, hydrophobicity and softness on biological response, and finally, we review the key points of surface modification strategies with organic, inorganic and biological materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1568026618666180810145234DOI Listing
November 2018

Adhesion, proliferation, and apoptosis in different molecular portraits of breast cancer treated with silver nanoparticles and its pathway-network analysis.

Int J Nanomedicine 2018 22;13:1081-1095. Epub 2018 Feb 22.

Laboratory of Immunology and Institute of Experimental and Clinical Therapeutics, Department of Physiology, University Center of Health Sciences, University of Guadalajara, Jalisco, Mexico.

Background: Silver nanoparticles (AgNPs) have attracted considerable attention due to the variety of their applications in medicine and other sciences. AgNPs have been used in vitro for treatment of various diseases, such as hepatitis B and herpes simplex infections as well as colon, cervical, and lung cancers. In this study, we assessed the effect on proliferation, adhesion, and apoptosis in breast cancer cell lines of different molecular profiles (MCF7, HCC1954, and HCC70) exposed to AgNPs (2-9 nm).

Methods: Breast cancer cell lines were incubated in vitro; MTT assay was used to assess proliferation. Adhesion was determined by real-time analysis with the xCELLingence system. Propidium iodide and fluorescein isothiocyanate-Annexin V assay were used to measure apoptosis. The transcriptome was assessed by gene expression microarray and Probabilistic Graphical Model (PGM) analyses.

Results: The results showed a decreased adhesion in breast cancer cell lines and the control exposed to AgNPs was noted in 24 hours (≤0.05). We observed a significant reduction in the proliferation of MCF7 and HCC70, but not in HCC1954. Apoptotic activity was seen in all cell lines exposed to AgNPs, with an apoptosis percentage of more than 60% in cancer cell lines and less than 60% in the control. PGM analysis confirmed, to some extent, the effects of AgNPs primarily on adhesion by changes in the extracellular matrix.

Conclusion: Exposure to AgNPs causes an antiproliferative, apoptotic, and anti-adhesive effect in breast cancer cell lines cultured in vitro. More research is needed to evaluate the potential use of AgNPs to treat different molecular profiles of breast cancer in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S152237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826086PMC
April 2018

Preparation of PLGA/Rose Bengal colloidal particles by double emulsion and layer-by-layer for breast cancer treatment.

J Colloid Interface Sci 2018 May 7;518:122-129. Epub 2018 Feb 7.

Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Guadalajara, Jalisco 44340, Mexico. Electronic address:

The use of colloidal particles (CPs) in the transport of drugs is developing rapidly thanks to its effectiveness and biosafety, especially in the treatment of various types of cancer. In this study Rose Bengal/PLGA CPs synthesized by double emulsion (W/O/W) and by electrostatic adsorption (layer-by-layer), were characterized and evaluated as potential breast cancer treatment. CPs were evaluated in terms of size, zeta potential, drug release kinetics and cell viability inhibition efficacy with the triple negative breast cancer cell line HCC70. The results showed that both types of CPs can be an excellent alternative to conventional cancer treatment by taking advantage of the enhanced permeation and retention (EPR) effect, manifested by solid tumors; however, the double emulsion CPs showed more suitable delivery times of up to 60% within two days, while layer-by-layer showed fast release of 50% in 90 min. Both types of CPs were capable to decrease cell viability, which encourage us to further testing in in vivo models to prove their efficacy and feasible use in the treatment of triple negative breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2018.02.013DOI Listing
May 2018

Evaluation of psychosocial aspects in participants of cancer genetic counseling.

Hered Cancer Clin Pract 2017 20;15:13. Epub 2017 Sep 20.

Programa de Asesoramiento Genético Oncológico, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 950 Sierra Mojada St., Independencia, 44340 Guadalajara, Jalisco Mexico.

Background: The instrument called "Hospital Anxiety and Depression Scale" (HADS) is frequently used to evaluate anxious and depressive symptomatology in patients who receive Cancer Genetic Counseling (CGC). However, this instrument cannot identify all of the psychosocial factors, such as the antecedents of the patients' emotional states or their concerns. The objective of the present research was to compare cases detected with psychosocial alterations by means of HADS and a Psychological Health Interview (PHI).

Methods: A transversal analytical design was used. One hundred ten participants were included (97.3% females and 2.7% males). The average age was 45 years ±10 years.

Results: The PHI identified twice the amount of participants with psychosocial alterations than did HADS, which only detected 43% of these participants.

Conclusions: The results of our study suggest that the PHI should be applied in addition to HADS to identify participants who would require psychological support due to recurrent concerns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13053-017-0073-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607594PMC
September 2017

Validation of Health Behavior and Stages of Change Questionnaire.

Breast Cancer (Dove Med Press) 2017 22;9:199-205. Epub 2017 Mar 22.

Department of Health Sciences, University Centre of Tonala, University of Guadalajara, Guadalajara.

Background: The transtheoretical model (TTM) has been widely used to promote healthy behaviors in different groups. However, a questionnaire has not yet been developed to evaluate the health behaviors that medical practitioners often consider in individuals with cancer or at a high risk of developing cancer.

Purpose: The aim of this study was to construct and validate the Health Behavior and Stages of Change Questionnaire (HBSCQ), which is based on the TTM and health recommendations related to risk and factors that protect against cancer.

Methods: Content validity was conducted in two phases (qualitative and quantitative). Item difficulty index, item discrimination index, and discrimination coefficient were obtained based on the classical test theory. Finally, Cronbach's alpha was used.

Results: Measure of concordance showed scores considered adequate and excellent. The item discrimination index obtained a rating of "excellent" and suggested the preservation of all items. The discrimination coefficient scores are >0.74. The global internal consistency of the HBSCQ was 0.384. HBSCQ specification between groups of internal consistency for the sample of men was 0.712 and that for the sample of women was 0.378.

Conclusion/implications For Practice: The HBSCQ represents a proposal for a fast, simple, and innovative screening test, which aims to identify persons who may benefit from interventions to promote health behaviors delimited to the stage of change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/BCTT.S129855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367771PMC
March 2017

The role of endothelial cells on islet function and revascularization after islet transplantation.

Organogenesis 2016 01 22;12(1):28-32. Epub 2016 Mar 22.

a Department of Physiology, Laboratory of Immunology, Tissue Engineering and Transplant , University Center for Health Sciences, University of Guadalajara , Mexico ;

Islet transplantation has become a widely accepted therapeutic option for selected patients with type 1 diabetes mellitus. However, in order to achieve insulin independence a great number of islets are often pooled from 2 to 4 pancreata donors. Mostly, it is due to the massive loss of islets immediately after transplant. The endothelium plays a key role in the function of native islets and during the revascularization process after islet transplantation. However, if a delayed revascularization occurs, even the remaining islets will also undergo to cell death and late graft dysfunction. Therefore, it is essential to understand how the signals are released from endothelial cells, which might regulate both differentiation of pancreatic progenitors and thereby maintenance of the graft function. New strategies to facilitate islet engraftment and a prompt revascularization could be designed to intervene and might lead to improve future results of islet transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15476278.2016.1165378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882122PMC
January 2016

Acculturation, Behavioral Factors, and Family History of Breast Cancer among Mexican and Mexican-American Women.

Womens Health Issues 2015 Sep-Oct;25(5):494-500. Epub 2015 Jul 17.

Moores Cancer Center, University of California, San Diego, La Jolla, California.

Background: Incidence rates for breast cancer are higher among Mexican-American (MA) women in the United States than women living in Mexico. Studies have shown higher prevalence of breast cancer risk factors in more acculturated than less acculturated Hispanic/Latinas in the United States. We compared the prevalence of behavioral risk factors and family history of breast cancer by level of acculturation and country of residence in women of Mexican descent.

Methods: Data were collected from 1,201 newly diagnosed breast cancer patients living in Mexico (n = 581) and MAs in the United States (n = 620). MA participants were categorized into three acculturation groups (Spanish dominant, bilingual, and English dominant); women living in Mexico were used as the referent group. The prevalence of behavioral risk factors and family history of breast cancer were assessed according to acculturation level, adjusting for age at diagnosis and education.

Results: In the adjusted models, bilingual and English-dominant MAs were significantly more likely to have a body mass index of 30 kg/m(2) or greater, consume more than one alcoholic beverage a week, and report having a family history of breast cancer than women living in Mexico. All three U.S. acculturation groups were significantly more likely to have lower total energy expenditure (≤533 kcal/d) than women in Mexico. English-dominant women were significantly less likely to ever smoke cigarettes than the Mexican group.

Conclusions: Our findings add to the limited scientific literature on the relationships among acculturation, health behavior, and family history of breast cancer in Mexican and MA women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.whi.2015.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739633PMC
July 2016

Differentially expressed microRNAs in postpartum breast cancer in Hispanic women.

PLoS One 2015 13;10(4):e0124340. Epub 2015 Apr 13.

Department of Family & Preventive Medicine, University of California San Diego, La Jolla, CA, United States of America.

The risk of breast cancer transiently increases immediately following pregnancy; peaking between 3-7 years. The biology that underlies this risk window and the effect on the natural history of the disease is unknown. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to be dysregulated in breast cancer. We conducted miRNA profiling of 56 tumors from a case series of multiparous Hispanic women and assessed the pattern of expression by time since last full-term pregnancy. A data-driven splitting analysis on the pattern of 355 miRNAs separated the case series into two groups: a) an early group representing women diagnosed with breast cancer ≤ 5.2 years postpartum (n = 12), and b) a late group representing women diagnosed with breast cancer ≥ 5.3 years postpartum (n = 44). We identified 15 miRNAs with significant differential expression between the early and late postpartum groups; 60% of these miRNAs are encoded on the X chromosome. Ten miRNAs had a two-fold or higher difference in expression with miR-138, miR-660, miR-31, miR-135b, miR-17, miR-454, and miR-934 overexpressed in the early versus the late group; while miR-892a, miR-199a-5p, and miR-542-5p were underexpressed in the early versus the late postpartum group. The DNA methylation of three out of five tested miRNAs (miR-31, miR-135b, and miR-138) was lower in the early versus late postpartum group, and negatively correlated with miRNA expression. Here we show that miRNAs are differentially expressed and differentially methylated between tumors of the early versus late postpartum, suggesting that potential differences in epigenetic dysfunction may be operative in postpartum breast cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124340PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395255PMC
April 2016

Family history of breast and ovarian cancer and triple negative subtype in hispanic/latina women.

Springerplus 2014 11;3:727. Epub 2014 Dec 11.

Moores Cancer Center, University of California San Diego, 3855 Health Sciences Dr., #0901, La Jolla, CA 92093-0901 USA ; Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA USA.

Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC than non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26-2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age <50 compared to ≥50 years for breast cancer in a first-degree relative (P-interaction = 0.14) and a first- or second-degree relative (P-interaction = 0.07). Findings suggest that familial breast cancers are associated with triple negative subtype, possibly related to BRCA mutations in Hispanic/Latina women, which are strongly associated with TNBC. Family history is an important tool to identify Hispanic/Latina women who may be at increased risk of TNBC, and could benefit from prevention and early detection strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/2193-1801-3-727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332916PMC
February 2015

Prolactin and prolactin receptor expression in cervical intraepithelial neoplasia and cancer.

Pathol Oncol Res 2015 Apr 3;21(2):241-6. Epub 2014 Jul 3.

Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

Prolactin receptor (PRLR) overexpression could play a role in tumorigenesis. The aim of this study was to determine prolactin (PRL) and PRLR expression in biopsies from patients with precursor lesions and uterine cervical cancer. PRLR expression was analyzed in 63 paraffin-embedded biopsies of uterine cervical tissue. In total, eleven low-grade squamous intraepithelial lesions (LSIL), 23 high-grade squamous intraepithelial lesions (HSIL), 21 uterine cervical cancers (UCC) and 8 normal epithelium (NE) were examined using immunoperoxidase staining and Western blot analysis. Additionally, PRL expression was identified in human cervical cancer serum and tissues. The PRLR expression was found to be significantly increased in cervical cancer in comparison with normal tissue and precursor lesions (P < 0.0003). The presence of the long isoform of the PRLR was observed only in cervical cancer tissues. Serum PRL levels were normal in all samples and local prolactin expression was similar in precursor lesions and cervical cancer by Western blot analysis. Our data suggest a possible role for PRLR in the progression of cervical cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12253-014-9814-6DOI Listing
April 2015

Development and Psychometric Assessment of the Measure of Globalization Influence on Health Risk (MGIHR) Among Mexican Women with Breast Cancer.

J Immigr Minor Health 2015 Aug;17(4):1025-32

Department of Family and Preventive Medicine, Moores UCSD Cancer Center, University of California, 3855 Health Sciences Drive, #0901, San Diego, La Jolla, CA, 92093-0901, USA,

Lacking in the literature are data addressing the extent to which changes in reproductive and lifestyle factors predispose women in developing nations to higher breast cancer rates, and the degree to which these are due to globalization influences. This article describes the development and psychometric assessment of an instrument intended to measure global, predominantly U.S., influences on breast cancer risk profile among women residing in Mexico. Using investigator consensus and a focus group methodology, the Measure of Globalization Influence on Health Risk (MGIHR) was developed and completed by 341 women. Psychometric analysis support the use of an 11-item Consumerism and Modernity scale and 7-item Reproductive Control and Gender Role scale. The MGIHR is a valid and reliable instrument for understanding changing lifestyle and reproductive factors for breast cancer risk and may provide a more complete understanding of breast cancer development and needed interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10903-014-0042-7DOI Listing
August 2015

Reproductive and hormonal risk profile according to language acculturation and country of residence in the Ella Binational Breast Cancer Study.

J Womens Health (Larchmt) 2014 Jun 29;23(6):532-40. Epub 2014 Jan 29.

1 Moores University of California San Diego Cancer Center, University of California , San Diego, La Jolla, California.

Background: We compared the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent.

Methods: To compare the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent, taking into account level of education, we analyzed data on 581 Mexican and 620 Mexican American (MA) women with a history of invasive breast cancer from the Ella Binational Breast Cancer Study. An eight-item language-based acculturation measure was used to classify MA women. Multivariate logistic regression was used to test associations between language acculturation, country of residence, and reproductive and hormonal risk factors.

Results: After adjustment for age and education, compared to women residing in Mexico, English-dominant MAs were significantly more likely to have an earlier age at menarche (<12 years; odds ratio [OR]=2.08; 95% confidence interval [CI], 1.30-3.34), less likely to have a late age at first birth (≥30 years; OR=0.49; 95% CI, 0.25-0.97), and less likely to ever breastfeed (OR=0.13; 95% CI, 0.08-0.21).

Conclusions: Differences in reproductive and hormonal risk profile according to language acculturation and country of residence are evident; some of these were explained by education. Results support continued efforts to educate Mexican and MA women on screening and early detection of breast cancer along with promotion of modifiable factors, such as breastfeeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jwh.2013.4498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046352PMC
June 2014

Reproductive factors, heterogeneity, and breast tumor subtypes in women of mexican descent.

Cancer Epidemiol Biomarkers Prev 2013 Oct 15;22(10):1853-61. Epub 2013 Aug 15.

Authors' Affiliations: Moores Cancer Center; Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, California; Arizona Cancer Center, University of Arizona, Tucson; Department of Surgery, Maricopa Medical Center, Phoenix, Arizona; Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine; University of Texas M.D. Anderson Cancer Center, Houston, Texas; Universidad of Guadalajara, Guadalajara; Instituto Tecnológico de Sonora, Ciudad Obregón; and Universidad of Sonora, Hermosillo, Mexico.

Background: Published data support the presence of etiologic heterogeneity by breast tumor subtype, but few studies have assessed this in Hispanic populations.

Methods: We assessed tumor subtype prevalence and associations between reproductive factors and tumor subtypes in 1,041 women of Mexican descent enrolled in a case-only, binational breast cancer study. Multinomial logistic regression comparing HER2(+) tumors and triple-negative breast cancer (TNBC) to luminal A tumors was conducted.

Results: Compared with women with luminal A tumors, those with a later age at first pregnancy were less likely to have TNBC [OR, 0.61; 95% confidence interval (CI), 0.39-0.95], whereas those with three or more full-term pregnancies were more likely to have TNBC (OR, 1.68; 95% CI, 1.10-2.55). A lower odds of TNBC was shown for longer menstruation duration, whether before first pregnancy (OR, 0.78; 95% CI, 0.65-0.93 per 10 years) or menopause (OR, 0.79; 95% CI, 0.69-0.91 per 10 years). Patients who reported breastfeeding for more than 12 months were over twice as likely to have TNBC than luminal A tumors (OR, 2.14; 95% CI, 1.24-3.68). Associations comparing HER2(+) with luminal A tumors were weak or nonexistent except for the interval between last full-term pregnancy and breast cancer diagnosis.

Conclusions: Findings show etiologic heterogeneity by tumor subtype in a population of Hispanic women with unique reproductive profiles.

Impact: Identification of etiologically distinct breast tumor subtypes can further improve our understanding of the disease and help provide personalized prevention and treatment regimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-13-0560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799795PMC
October 2013

Hypothesized role of pregnancy hormones on HER2+ breast tumor development.

Breast Cancer Res Treat 2013 Jan 8;137(1):237-46. Epub 2012 Nov 8.

School of Public Health, University of California, Berkeley, Berkeley, CA, USA.

Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (≤10 or >10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies ≥1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2- cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of ≤10 years (OR = 1.68; 95 % CI, 1.12-2.52). The effect was present across all source populations and independent of the HR status of the HER2+ tumor. Adjusting for age at diagnosis (≤45 or >45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08-2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-012-2313-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054812PMC
January 2013

Increased expression of the prolactin receptor is associated with malignant laryngeal tumors.

Exp Ther Med 2012 Apr 30;3(4):603-607. Epub 2012 Jan 30.

Departments of Physiology, and.

The altered expression of the prolactin receptor (PRLR) has been associated with the development of various types of cancer, particularly breast, prostate and endometrial cancer. However, in laryngeal tumors, the expression of PRLR has not yet been documented. The aim of this study was to determine the expression and localization of PRLR in laryngeal cancer (LC) in comparison with recurrent respiratory papillomatosis (RRP). PRLR expression was analyzed in 48 paraffin-embedded tissues (18 RRP and 30 laryngeal cancer tissues) by immunoperoxidase staining. Furthermore, PRLR expression was evaluated in ten samples from each group by Western blot analysis and quantitative real-time PCR. PRLR was observed in all laryngeal tumors at different intensities. PRLR overexpression was significantly associated (P<0.005) with LC. The staining pattern was homogeneous, mainly cytoplasmic, and confined to the tumor area. We found increased expression of different isoforms in LC in comparison with RRP. Our results suggest a possible role of PRL/PRLR in the development of LC. PRLR may be useful as a target for further investigations in laryngeal tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2012.464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438611PMC
April 2012

Association between parity and obesity in Mexican and Mexican-American women: findings from the Ella binational breast cancer study.

J Immigr Minor Health 2013 Apr;15(2):234-43

Moores UCSD Cancer Center, University of California, San Diego, 3855 Health Sciences Drive, #0901, La Jolla, CA 92093-0901, USA.

Obesity at diagnosis of breast cancer is associated with higher all-cause mortality and treatment-associated toxicities. We evaluated the association between parity and obesity in the Ella study, a population of Mexican and Mexican-American breast cancer patients with high parity. Obesity outcomes included body mass index (BMI) ≥30 kg/m(2), waist circumference (WC) ≥35 in (88 cm), and waist-to-hip-ratio (WHR) ≥0.85. Prevalence of obesity ([BMI] ≥ 30 kg/m(2)) was 38.9 %. For WC, the multivariate odds ratio (OR) (95 % confidence interval [CI]) for having WC ≥ 35 inches in women with ≥4 pregnancies relative to those with 1-2 pregnancies was 1.59 (1.01-2.47). Higher parity (≥4 pregnancies) was non-significantly associated with high BMI (OR = 1.10; 95 % CI 0.73-1.67). No positive association was observed for WHR. Our results suggest WC is independently associated with high parity in Hispanic women and may be an optimal target for post-partum weight loss interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10903-012-9649-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469728PMC
April 2013

Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications.

BMC Immunol 2012 Feb 8;13. Epub 2012 Feb 8.

Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

Background: Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK) cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down-modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity.

Results: We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT). Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells.

Conclusions: Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2172-13-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364150PMC
February 2012

YKL-40 expression in CD14⁺ liver cells in acute and chronic injury.

World J Gastroenterol 2011 Sep;17(33):3830-5

Department of Physiology, CUCS, University of Guadalajara, Guadalajara, Jalisco 44340, México.

Aim: To demonstrate that CD14⁺ cells are an important source of the growth factor YKL-40 in acute and chronic liver damage.

Methods: Rats were inoculated with one dose of CCl(4) to induce acute damage. Liver biopsies were obtained at 0, 6, 12, 24, 48 and 72 h. For chronic damage, CCl(4) was administered three days per week for 6 or 8 wk. Tissue samples were collected, and cellular populations were isolated by liver digestion and purified by cell sorting. YKL-40 mRNA and protein expression were evaluated by real-time polymerase chain reaction and western blot.

Results: Acute liver damage induced a rapid increase of YKL-40 mRNA beginning at 12 h. Expression peaked at 24 h, with a 26-fold increase over basal levels. By 72 h however, YKL-40 expression levels had nearly returned to control levels. On the other hand, chronic damage induced a sustained increase in YKL-40 expression, with 7- and 9-fold higher levels at 6 and 8 wk, respectively. The pattern of YKL-40 expression in different subpopulations showed that CD14⁺ cells, which include Kupffer cells, are a source of YKL-40 after acute damage at 72 h [0.09 relative expression units (REU)] as well as after chronic injury at 6 wk (0.11 REU). Hepatocytes, in turn, accounted for 0.06 and 0.01 REU after 72 h (acute) or 6 wk (chronic), respectively. The rest of the CD14⁻ cells (including T lymphocytes, B lymphocytes, natural killer and natural killer T cells) yielded 0.07 and 0.15 REU at 72 h and 6 wk, respectively. YKL-40 protein expression in liver was detected at 72 h as well as 6 and 8 wk, with the highest expression relative to controls (11-fold; P ≤ 0.05) seen at 6 wk. Macrophages were stimulated by lipopolysaccharide. We demonstrate that under these conditions, these cells showed maximum expression of YKL-40 at 12 h, with P < 0.05 compared with controls.

Conclusion: Hepatic CD14⁺ cells are an YKL-40 mRNA and protein source in acute and chronic liver injury, with expression patterns similar to growth factors implicated in inflammation-fibrogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v17.i33.3830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181445PMC
September 2011

MHC class I-related chain A and B ligands are differentially expressed in human cervical cancer cell lines.

Cancer Cell Int 2011 Jun 1;11:15. Epub 2011 Jun 1.

División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.

Background: Natural killer (NK) cells are an important resource of the innate immune system directly involved in the spontaneous recognition and lysis of virus-infected and tumor cells. An exquisite balance of inhibitory and activating receptors tightly controls the NK cell activity. At present, one of the best-characterized activating receptors is NKG2D, which promotes the NK-mediated lysis of target cells by binding to a family of cell surface ligands encoded by the MHC class I chain-related (MIC) genes, among others. The goal of this study was to describe the expression pattern of MICA and MICB at the molecular and cellular levels in human cervical cancer cell lines infected or not with human papillomavirus, as well as in a non-tumorigenic keratinocyte cell line.

Results: Here we show that MICA and MICB exhibit differential expression patterns among HPV-infected (SiHa and HeLa) and non-infected cell lines (C33-A, a tumor cell line, and HaCaT, an immortalized keratinocyte cell line). Cell surface expression of MICA was higher than cell surface expression of MICB in the HPV-positive cell lines; in contrast, HPV-negative cells expressed lower levels of MICA. Interestingly, the MICA levels observed in C33-A cells were overcome by significantly higher MICB expression. Also, all cell lines released higher amounts of soluble MICB than of soluble MICA into the cell culture supernatant, although this was most pronounced in C33-A cells. Additionally, Real-Time PCR analysis demonstrated that MICA was strongly upregulated after genotoxic stress.

Conclusions: This study provides evidence that even when MICA and MICB share a high degree of homology at both genomic and protein levels, differential regulation of their expression and cell surface appearance might be occurring in cervical cancer-derived cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1475-2867-11-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120738PMC
June 2011

The distribution of CD56(dim) CD16+ and CD56(bright) CD16- cells are associated with prolactin levels during pregnancy and menstrual cycle in healthy women.

Am J Reprod Immunol 2011 Apr 6;65(4):433-7. Epub 2010 Sep 6.

Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, CUCS, Universidad de Guadalajara, Jalisco, México.

Problem: The pregnancy and menstrual cycle (MC) are the main physiologic events linked to the human reproduction. An adequate neuroendocrine axis is mandatory for the homeostasis in both events. To analyze the distribution of NK, T, Treg cells, expression of their receptors and to associate with hormone levels in pregnant and MC in healthy women.

Method Of Study: We studied two groups of healthy women: 13 pregnant women followed up at 1st, 2nd and 3rd trimesters and 11 women in the 5th and 21st day of the MC. The distribution of NK, T, Treg cells population, expression of their receptors and hormone levels were quantified.

Results: In pregnant women, we found an association of NK cells CD56(dim) CD16(+) with prolactin levels. This finding was also was observed for CD56(brigthCD16-) being statistical significant during 1st trimester for both subpopulations. During MC, correlation of CD56(dim) CD16(+) , CD56(bright) CD16(-) cells with prolactin in follicular and luteal phase was found.

Conclusion: This is the first report where these cell subpopulations have been analyzed prospectively. Even we can argue the random effect for the small number of women is interesting that prolactin showed the more consistent correlation with CD56(dim) CD16(+) , CD56(brigth) CD16(-) cells during both events studied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0897.2010.00916.xDOI Listing
April 2011

Immunobiology of HPV Infection.

Arch Med Res 2009 Aug 25;40(6):443-8. Epub 2009 Jul 25.

Departamento de Biología Celular, Cinvestav-IPN, México D.F., México.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arcmed.2009.05.003DOI Listing
August 2009

Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions.

BMC Cancer 2009 Jun 16;9:186. Epub 2009 Jun 16.

Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No 950, Colonia Independencia, Guadalajara, Jalisco, Mexico.

Background: Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection.

Methods: NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays.

Results: We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients.

Conclusion: Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2407-9-186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704222PMC
June 2009

[Lymphocyte subsets and preeclampsia].

Ginecol Obstet Mex 2008 Jun;76(6):327-35

Centro Médico Nacional de Occidente, UMAE, Hospital de Especialidades, Unidad de Investigación Médica en Epidemiología Clínica, Guadalajara, Jalisco, México.

Background: Preeclampsia origin has no conclusive explanation. As part of its etiology it has been proposed immunologic disorders. This work explores several lymphocytes subsets and postulates possible mechanisms involved in a lost of immune tolerance in this entity.

Objective: To compare cellular populations of CD3+ CD56+, CD4+ CD25+, T lymphocytes (CD4+ and CD8+) and NK cells subsets in preeclamptic and pregnant healthy women.

Patients And Methods: Through flow cytometry antibodies, peripheral blood mononuclear cells were obtained from both groups of patients. CD3+ CD56+, CD4+ CD25+, T lymphocytes (CD4+ and CD8+) and NK cells were identified. Mean and standard deviation, Student ttest and Pearson correlation were calculated to analyze differences between groups and correlation between mean blood pressure and different lymphocytes subsets; p < 0.05 was considered significant.

Results: CD3+ CD56+ cells percentage was lower in preeclamptic patients (2.7 vs 6.1%; p < 0.002), CD4+ CD25+ cells percentage tend to be lower too (22.11 vs 33.86; p = NS). Mean blood pressure shown negative correlation with CD3+ CD56+ cells percentage (rp - 0.666; p = 0.001) and with CD25 on CD4+ T lymphocytes surface (rp - 0.526; p < 0.025).

Conclusions: Based on the association between mean blood pressure and lymphocytes percentage for these two cellular subsets, data obtained suggest that CD3+ CD56+ and CD4+ CD25+ cells play an important role in preeclampsia development.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2008