Sandra Ampuero | University of Chile (original) (raw)

Papers by Sandra Ampuero

Cancer Epidemiology, Biomarkers & Prevention

More than 18 types of human papillomavirus (HPV) are associated with cervical cancer, the relativ... more More than 18 types of human papillomavirus (HPV) are associated with cervical cancer, the relative importance of the HPV types may vary in different populations. Objective: To investigate the types of HPV, age distribution, and risk factors for HPV infection in women from Santiago, Chile. Methods: We interviewed and obtained two cervical specimens from a population-based random sample of 1,038 sexually active women (age range, 15-69 years). Specimens were tested for the presence of HPV DNA using a GP5+/6+ primer-mediated PCR and for cervical cytologic abnormalities by Papanicolaou smears. Results: 122 women tested positive for HPV DNA, 87 with high risk types (HR), and 35 with low risks (LR) only. Standardized prevalence of HPV DNA was 14.0% [95% confidence interval (95% CI), 11.5-16.4]. HR HPV by age showed a J reverse curve, whereas LR HPV showed a U curve, both statistically significant in comparison with no effect or with a linear effect. We found 34 HPV types (13 HR and 21 LR);...

Human Reproduction, Jul 1, 1997

nursing women and their physicians are sceptical about its use de Reproducción y Desarrollo, Facu... more nursing women and their physicians are sceptical about its use de Reproducción y Desarrollo, Facultad de Ciencias Biológicas, and resort to other contraceptive methods, even if unnecessary.

Biological Research, 2003

Storey et al. (1998) implicated the proline/argine polymorphism of the codon 72 of the tumor-supp... more Storey et al. (1998) implicated the proline/argine polymorphism of the codon 72 of the tumor-suppressor gene p53 in the development of cervical cancer (CC) with the observation that the p53 protein is more efficiently inactivated by the E6 oncoprotein of human papillomavirus in p53 arginine as compared with its proline isoform. These authors further noted that in the United Kingdom, individuals homozygous for the arginine allele were several times more susceptible to HPV-associated tumorigenesis that proline/arginine heterozygotes. Subsequent studies in different countries failed to unanimously confirm this association. Motivated by the high incidence of CC in Chile, we undertook a case control study obtaining the following frequencies for genotypes PP, AP and AA in 60 ICC cases and 53 carefully selected controls: 0.067, 0.250, 0.683 and 0.075, 0.453, 0.472 respectively. A significant difference (X 2 = 3.19 p < 0.02) and an odds ratio of 2.62 supported Storey et al (1998)'s results. In addition, rejecting previous hypotheses about the world distribution of the p53 codon 72 polymorphism, we conclude that this distribution most likely represents ancient human dispersal routes. Several methodological and biological explanations for the results obtained in previous negative association studies are briefly discussed.

Cancer genetics and cytogenetics, Oct 1, 2007

Several studies have reported that mutations in genes involved in maintenance of genome integrity... more Several studies have reported that mutations in genes involved in maintenance of genome integrity may be responsible for increased cancer risk. Human RAD51, known to function in DNA repair, interacts with a number of proteins implicated in breast cancer (BC), including BRCA1 and BRCA2. Few studies have investigated the role of RAD51 gene variations in familial BC. To detect potential novel gene defects that may contribute to hereditary BC susceptibility, 143 patients belonging to 143 Chilean families tested for BRCA1 and BRCA2 mutations were screened for mutations in RAD51, using conformational sensitive gel electrophoresis (CSGE) and DNA sequencing. No mutations were detected in the exon or splice-boundary regions of the RAD51 gene in these families. The RAD51 135G>C polymorphism (c.-98G>C, rs1801320) was studied in a case-control design, to evaluate its possible association with BC susceptibility. The frequency of the RAD51 135C allele was established in 143 cases and 247 controls, u

Infection, Genetics and Evolution, Jun 1, 2013

Respiratory syncytial virus (RSV) infection has been associated to recurrent wheezing, but pathog... more Respiratory syncytial virus (RSV) infection has been associated to recurrent wheezing, but pathogenic mechanisms are unclear. Interleukin-4/Interleukin-13 (IL-4/IL-13) pathway is involved in both conditions. A common host genetic susceptibility may exist in patients whom RSV will trigger severe illness and those who develop recurrent wheezing. Objective: To assess, by a candidate-gene approach, whether genetic polymorphisms in IL-4/IL-13 pathway are associated with RSV infection severity and its outcome in Chilean children. A cohort of 118 RSV-infected infants was analyzed and followed for one year. Severity of acute infection and later recurrent wheezing were characterized. Alleles and genotypes frequencies were determined for two SNP in each of the genes IL-4, IL-13 and IL-4Ra. Association tests and interaction analyses were performed. Enrollment included 60 moderate and 58 severe cases. Two SNP were found associated to severity during acute infection in IL-4Ra gene (Gln551Arg, Ile50Val). The follow up was completed in 71% of patients (84/ 118). Later recurrent wheezing was 54% in severe group, versus 31% in moderate cases (p = 0.035). In relation to outcome, allele Ile50 in IL-4Ra was more frequent in patients with moderate disease and no wheezing outcome. A common protector genotype is proposed for Chilean children: IL-4Ra Ile/Ile. Conclusion: Genetic variations in the host are associated to infection severity and outcome. A common genetic background might be influencing both pathologies.

In order to identify differences in clinical, histopathology and virology data of patients with e... more In order to identify differences in clinical, histopathology and virology data of patients with external condylomata acuminata (ECA) by HIV status, 47 HIV positive patients and 42 HIV negative patients were enrolled. Socio-demographic and clinical data was recorded. Histopathology study and HPV detection (Roche Linear Array genotyping assay) were performed. HIV positive patients were mainly single, MSM, with history of STI, multiple sexual partners, receiving antiretroviral therapy and with recurrent peri-anal ECA. HPV-16 and HPV-61 were associated to this group while HPV-6 was found in HIV negative patients with ECA. Intraepithelial neoplasia (IEN) was found in 5.6% of patients, associated to HIV and HPV-16. We found differences in socio-demographic characteristics and HPV genotypes in patients with ECA by HIV status. The association of high grade IEN with HIV infection makes evident the need of defined parameters as markers for early cancer diagnosis.

Human adenoviruses are one of the most important pathogens detected in acute respiratory diseases... more Human adenoviruses are one of the most important pathogens detected in acute respiratory diseases in pediatrics and immunocompromised patients. In 1953, Wallace Rowe described it for the first time in oropharyngeal lymphatic tissue. To date, more than 85 types of HAdV have been described, with different cellular tropisms. They can cause respiratory and gastrointestinal symptoms, even urinary tract inflammation, although most infections are asymptomatic. However, there is a population at risk that can develop serious and even lethal conditions. These viruses have a double-stranded DNA genome, 25-48 kbp, 90 nm in diameter, without a mantle, stable in the environment, and resistant to fat-soluble detergents. Currently the diagnosis is made with lateral flow immunochromatography or molecular biology through a polymerase chain reaction. The objective of this review is to recognize the variability of HAdV, the pandemic potential that a recombinant could present between HAdV-3 and 7 viral ...

European Journal of Human Genetics 9(Suppl, May 7, 2001

Scientific Reports

Community-acquired pneumonia (CAP) is a worldwide leading cause of death. Recognized risk factors... more Community-acquired pneumonia (CAP) is a worldwide leading cause of death. Recognized risk factors in some severe cases have not been identified. Lymphocytopenia has been frequently described in CAP. Since IL-7, membrane-bound receptor (IL7Rα;CD127) and soluble IL7Rα (sIL7R) are critical in lymphocytes homeostasis, in this work we aimed to evaluate the involvement of the IL-7/IL7Rα axis in the severity of adult CAP, since it has not been explored. The IL7Rα SNPs rs6897932, rs987106, and rs3194051 SNPs in IL7α were genotyped, the systemic expression of the IL7R gene, sIL7R, IL-7, and levels of peripheral IL7Rα+ T lymphocytes were quantified in 202 hospitalized CAP cases. rs3194051GG was more frequent in non-survivors than in survivors; rs987106TT was more frequent and rs3194051AA less frequent in patients at intensive care unit (ICU) than in those not admitted to ICU. IL7Rα gene expression was lower in non-survivors than in survivors, and in severe than in mild cases. CD3+CD127+ lymph...

Acta Veterinaria Scandinavica, 2006

Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Centra... more Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime."

Acta virologica, 2018

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infection i... more Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infection in infants. Winter outbreaks in Chile result in 5% of infected children hospitalized, with 0.01% mortality. Increased evidence indicates that viral and host factors modulate the severity of infection. Using DNA microarrays, we characterized the genome-wide transcriptional response of lung mucoepidermoid cells (NCI-H292) at 0, 24, 48, 72 and 96 hours post-infection (hpi) with a single dose of RSV/A. During the whole studied period, a bi-phasic gene expression profile was observed by a total of 330 differentially expressed genes. About 60% of them were up-regulated between 24-72 hpi and then turned-off at 96 hpi. This transient, early gene expression pattern was significantly enriched in biological processes like interferon signaling, antigen processing and presentation, double-stranded RNA binding and chemokine activity. We detected 27 common genes up-regulated between 24-72 hpi, from which IFIT1, IFI44, MX1, CXCL11 and OAS1 had the highest expression. The second pattern comprised over 120 genes, which remained silenced until 72 hpi, but were steeply up-regulated by 96 hpi. Biological processes of this late-response profile included cell cycle division and microtubule cytoskeleton organization. Conversely, the genes belonging to virus response pathway showed a decreased expression at 96 hpi. We conclude that RSV induces an early innate immune activation profile response until 72 hpi. Thereafter, the viral response is inhibited, leading to host cell recovery. The presented cellular model allows to study the specific pathways involved in elimination of infection at prolonged time intervals and their subsequent analysis in severe RSV disease of infants and/or older adults.

Biological Research

Background Driver mutations are the genetic components responsible for tumor initiation and progr... more Background Driver mutations are the genetic components responsible for tumor initiation and progression. These variants, which may be inherited, influence cancer risk and therefore underlie many familial cancers. The present study examines the potential association between SNPs in driver genes SF3B1 (rs4685), TBX3 (rs12366395, rs8853, and rs1061651) and MAP3K1 (rs72758040) and BC in BRCA1/2-negative Chilean families. Methods The SNPs were genotyped in 486 BC cases and 1258 controls by TaqMan Assay. Results Our data do not support an association between rs4685:C > T, rs8853:T > C, or rs1061651:T > C and BC risk. However, the rs12366395-G allele (A/G + G/G) was associated with risk in families with a strong history of BC (OR = 1.2 [95% CI 1.0–1.6] p = 0.02 and OR = 1.5 [95% CI 1.0–2.2] p = 0.02, respectively). Moreover, rs72758040-C was associated with increased risk in cases with a moderate-to-strong family history of BC (OR = 1.3 [95% CI 1.0–1.7] p = 0.02 and OR = 1.3 [95% ...

Revista médica de Chile, 2021

Biomolecules, 2020

In middle-aged women, the decline of ovarian follicle reserve below a critical threshold marks me... more In middle-aged women, the decline of ovarian follicle reserve below a critical threshold marks menopause, leading to hormonal, inflammatory, and metabolic changes linked to disease. The highest incidence and mortality of sporadic ovarian cancer (OC) occur at post-menopause, while OC risk is reduced by full-term pregnancies during former fertile life. Herein, we investigate how parity history modulates the ovarian transcriptome related to such declining follicle pool and systemic inflammation in reproductively-aged mice. Female C57BL/6 mice were housed under multiparous and virgin (nulliparous) breeding regimens from adulthood until estropause. The ovaries were then subjected to follicle count and transcriptional profiling, while a cytokine panel was determined in the sera. As expected, the follicle number was markedly decreased just by aging. Importantly, a significantly higher count of primordial and total follicles was observed in aged multiparous relative to aged virgin ovaries. ...

BMC Genomics, 2016

Background: Based in epidemiological evidence, repetitive ovulation has been proposed to play a r... more Background: Based in epidemiological evidence, repetitive ovulation has been proposed to play a role in the origin of ovarian cancer by inducing an aberrant wound rupture-repair process of the ovarian surface epithelium (OSE). Accordingly, long term cultures of isolated OSE cells undergo in vitro spontaneous transformation thus developing tumorigenic capacity upon extensive subcultivation. In this work, C57BL/6 mouse OSE (MOSE) cells were cultured up to passage 28 and their RNA and DNA copy number profiles obtained at passages 2, 5, 7, 10, 14, 18, 23, 25 and 28 by means of DNA microarrays. Gene ontology, pathway and network analyses were focused in passages earlier than 20, which is a hallmark of malignancy in this model. Results: At passage 14, 101 genes were up-regulated in absence of significant DNA copy number changes. Among these, the top-3 enriched functions (>30 fold, adj p < 0.05) comprised 7 genes coding for centralspindlin, chromosome passenger and minichromosome maintenance protein complexes. The genes Ccnb1 (Cyclin B1), Birc5 (Survivin), Nusap1 and Kif23 were the most recurrent in over a dozen GO terms related to the mitotic process. On the other hand, Pten plus the large non-coding RNAs Malat1 and Neat1 were among the 80 down-regulated genes with mRNA processing, nuclear bodies, ER-stress response and tumor suppression as relevant terms. Interestingly, the earliest discrete segmental aneuploidies arose by passage 18 in chromosomes 7, 10, 11, 13, 15, 17 and 19. By passage 23, when MOSE cells express the malignant phenotype, the dysregulated gene expression repertoire expanded, DNA imbalances enlarged in size and covered additional loci. Conclusion: Prior to early aneuploidies, overexpression of genes coding for the mitotic apparatus in passage-14 pre-malignant MOSE cells indicate an increased proliferation rate suggestive of replicative stress. Concomitant down-regulation of nuclear bodies and RNA processing related genes suggests altered control of nuclear RNA maturation, features recently linked to impaired DNA damage response leading to genome instability. These results, combined with cytogenetic analysis by other authors in this model, suggest that transcriptional profile at passage 14 might induce cytokinesis failure by which tetraploid cells approach a near-tetraploid stage containing primary chromosome aberrations that initiate the tumorigenic drive.

The Journal of Clinical Endocrinology & Metabolism, 1994

In our population, only half of fully nursing women remain amenorrheic 6 months postpartum. The o... more In our population, only half of fully nursing women remain amenorrheic 6 months postpartum. The other half recover their menstrual cycles between 90-180 days postpartum in spite of a high suckling frequency and elevated immunoreactive PRL (IR-PRL) concentrations. To further investigate the association of PRL with the recovery of ovarian function, we compared PRL bioactivity (BIO-PRL) 3-4 months postpartum in fully nursing amenorrheic women who subsequently experienced long (&amp;gt; 180 days; n = 5) or short (&amp;lt; 180 days; n = 5) lactational amenorrhea. In the present study, BIO-PRL in plasma was measured by the Nb2 lymphoma cell assay in samples taken before and 30 min after a suckling episode at 0800, 1600 and 2400 h. Women in the long amenorrhea group had higher overall mean BIO-PRL (mean +/- SE, 129.9 +/- 12.1 micrograms/L) than nursing women in the short amenorrhea group (66.6 +/- 5.2 micrograms/L; P &amp;lt; 0.05). Mean basal values were similar, but the women in the long amenorrhea group had more BIO-PRL in response to suckling (160.1 +/- 4.0 vs. 71.9 +/- 6.7 micrograms/L; P &amp;lt; 0.05). Compared with their respective basal values, nursing women in the long amenorrhea group demonstrated increased BIO-PRL in response to suckling, whereas the other group did not. The relationships between BIO-PRL and IR-PRL were similar in the two groups of nursing women before suckling. However, after suckling, the long amenorrhea group had significantly higher BIO-PRL levels than IR-PRL levels (P &amp;lt; 0.05, by likelihood test) than the short amenorrhea group. This suggests that suckling differentially changes in each group either the composition of PRL present or substances that may modify the bioactivity of PRL in plasma.

Infection, Genetics and Evolution, 2011

Cancer Genetics and Cytogenetics, 2006

A sample of 64 high-risk breast and/or ovarian cancer families from Chile were screened for germl... more A sample of 64 high-risk breast and/or ovarian cancer families from Chile were screened for germline mutations in the coding sequences and exon-intron boundaries of BRCA1 (MIN no. 113705) and BRCA2 (MIN no. 600185) genes using conformation-sensitive gel electrophoresis, and the mutations found were confirmed with direct sequencing. Seven families (10.9%) were found to carry BRCA1 mutations and three families (4.7%) had BRCA2 mutations. Six different pathogenic mutations were detected in BRCA1, four that had been reported previously (c.187_188delAG; c.300T/ G, c.3450_3453delCAAG and IVS17-1G/A) and two novel mutations (c.2605_2606delTT and c.4185_4188delCAAG). In BRCA2, we found three different pathogenic mutations, two previously described (c.6174delT and c.6503_6504delTT) and one novel mutation (c.5667delT). We also identified nine variants of unknown significance (five in BRCA1 and four in BRCA2). These findings indicate that the Chilean population has a heterogeneous spectrum of prevalent BRCA mutations. Given the results obtained in our study, the screening of the entire BRCA1 and BRCA2 coding regions is necessary for the molecular genetic testing of Chilean high-risk breast/ovarian cancer patients. To our knowledge, this is the first genetic study of BRCA gene mutations conducted in Chile. The Chilean population has a well-known admixed Amerindian-Caucasian ratio and, therefore, our findings are not only important per se, but they constitute the basis for improved and more specific genetic counselling, as well as to support for preventive campaigns geared toward the Chilean population.