Ricardo López-Romero

Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways

BackgroundCervical carcinoma (CC) is a leading cause of death among women worldwide. Human papilloma virus (HPV) is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways.ResultsWe found 2,067 genes significantly up or down-modulated (at least 2-fold) in tumor clinical samples compared to normal tissues, representing ~3.7% of analyzed genes. Cervical carcinoma was associated with an important up-regulation of Wnt signaling pathway, which was validated by in situ hybridization in clinical samples. Other up-regulated pathways were those of calcium signaling and MAPK signaling, as well as cell cycle-related genes. There was down-regulation of focal adhesion, TGF-β signaling, among other metabolic pathways.ConclusionThis analysis of HPV 16 tumors transcriptome could be useful for the identification of genes and molecular pathways involved in the pathogenesis of cervical carcinoma. Understanding the possible role of these proteins in the pathogenesis of CC deserves further studies.

Human papillomavirus genotypes among females in Mexico: a study from the Mexican institute for social security.

BACKGROUND The aetiological relationship between human papillomavirus (HPV) infection and cervical cancer (CC) is widely accepted. Our goal was to determine the prevalence of HPV types in Mexican women attending at the Mexican Institute for Social Security from different areas of Mexico. MATERIALS AND METHODS DNAs from 2,956 cervical samples were subjected to HPV genotyping: 1,020 samples with normal cytology, 931 with low-grade squamous intraepithelial lesions (LGSIL), 481 with high grade HGSIL and 524 CC. RESULTS Overall HPV prevalence was 67.1%. A total of 40 HPV types were found; HPV16 was detected in 39.4% of the HPV-positive samples followed by HPV18 at 7.5%, HPV31 at 7.1%, HPV59 at 4.9%, and HPV58 at 3.2%. HPV16 presented the highest prevalence both in women with altered or normal cytology and HPV 18 presented a minor prevalence as reported worldwide. The prevalence ratio (PR) was calculated for the HPV types. The analysis of PR showed that HPV16 presents the highest association with CC, HPV 31, -33, -45, -52 and -58 also demonstrating a high association. CONCLUSIONS The most prevalent HPV types in cervical cancer samples were -16, -18, -31, but it is important to note that we obtained a minor prevalence of HPV18 as reported worldwide, and that HPV58 and -52 also were genotypes with an important prevalence in CC samples. Determination of HPV genotypes is very important in order to evaluate the impact of vaccine introduction and future cervical cancer prevention strategies.

Splice variants of zinc finger protein 695 mRNA associated to ovarian cancer

BackgroundStudies of alternative mRNA splicing (AS) in health and disease have yet to yield the complete picture of protein diversity and its role in physiology and pathology. Some forms of cancer appear to be associated to certain alternative mRNA splice variants, but their role in the cancer development and outcome is unclear.MethodsWe examined AS profiles by means of whole genome exon expression microarrays (Affymetrix GeneChip 1.0) in ovarian tumors and ovarian cancer-derived cell lines, compared to healthy ovarian tissue. Alternatively spliced genes expressed predominantly in ovarian tumors and cell lines were confirmed by RT-PCR.ResultsAmong several significantly overexpressed AS genes in malignant ovarian tumors and ovarian cancer cell lines, the most significant one was that of the zinc finger protein ZNF695, with two previously unknown mRNA splice variants identified in ovarian tumors and cell lines. The identity of ZNF695 AS variants was confirmed by cloning and sequencing of the amplicons obtained from ovarian cancer tissue and cell lines.ConclusionsAlternative ZNF695 mRNA splicing could be a marker of ovarian cancer with possible implications on its pathogenesis.

A non-invasive tool for detecting cervical cancer odor by trained scent dogs

BackgroundCervical Cancer (CC) has become a public health concern of alarming proportions in many developing countries such as Mexico, particularly in low income sectors and marginalized regions. As such, an early detection is a key medical factor in improving not only their population’s quality of life but also its life expectancy. Interestingly, there has been an increase in the number of reports describing successful attempts at detecting cancer cells in human tissues or fluids using trained (sniffer) dogs. The great odor detection threshold exhibited by dogs is not unheard of. However, this represented a potential opportunity to develop an affordable, accessible, and non-invasive method for detection of CC.MethodsUsing clicker training, a male beagle was trained to recognize CC odor. During training, fresh CC biopsies were used as a reference point. Other samples used included cervical smears on glass slides and medical surgical bandages used as intimate sanitary pads by CC patients. A double-blind procedure was exercised when testing the beagle’s ability to discriminate CC from control samples.ResultsThe beagle was proven able to detect CC-specific volatile organic compounds (VOC) contained in both fresh cervical smear samples and adsorbent material samples. Beagle’s success rate at detecting and discriminating CC and non-CC odors, as indicated by specificity and sensitivity values recorded during the experiment, stood at an overall high (>90%). CC-related VOC in adsorbent materials were detectable after only eight hours of use by CC patients.ConclusionPresent data suggests different applications for VOC from the uterine cervix to be used in the detection and diagnosis of CC. Furthermore, data supports the use of trained dogs as a viable, affordable, non-invasive and, therefore, highly relevant alternative method for detection of CC lesions. Additional benefits of this method include its quick turnaround time and ease of use while remaining highly accurate and robust.

Volatolome of the Female Genitourinary Area: Toward the Metabolome of Cervical Cancer

BACKGROUND AND AIMS Different Volatile Organic Compounds (VOCs) obtained from several human fluids (volatolome) has been reported as potential biomarkers for a great variety of diseases including cancer. At present, volatolomic profile data of the female genital area is scarce. METHODS To identify the VOCs related to the female genitourinary area of healthy and Cervical Cancer (CC)-affected women used a pad, as a non-invasive tool for sample gathering was necessary. Used pads were analyzed by Gas Chromatography-Mass Spectrometry. The data were subjected to Principal Component Analysis looking for a possible spectrum of VOCs that could help identify CC-affected patients. The diagnostic role of the VOCs was validated through Receiver Operating Characteristic (ROC) analysis. The area below the curve and the diagnostic sensitivity and specificity values were also evaluated. RESULTS The data showed great differences between female cancer and healthy patients groups; most of these VOCs belonging to the alkanes chemical classes. A group of VOCs were identified as common among CC patients, while others VOCs for healthy females. The ROC curve showed an optimal reach to diagnosis (89%), returning a 93% rate for sensitivity and specificity, indicating the VOCs identified in the samples could differentiate cancer patients from healthy females. CONCLUSIONS In summary, we have detected and identified specific VOCs from healthy women that are not present in CC-affected females and VOCs specific of CC-affected women. We are strengthening our findings to aid in the detection of VOCs that are potential biomarkers for cervical tumors.

Toward a Non-Empirical Treatment for Rheumatoid Arthritis Based on Its Molecular Pathogenesis

Rheumatoid arthritis (RA) is a chronic, disabling disease that affects individuals during the productive years of their lives. Modern treatment for RA includes the so-called “biologic” therapy, which is based on recombinant proteins that modify the biologic processes. These agents have potent therapeutic effects and different mechanisms of action. Nevertheless, therapeutic failure still prevails. Treatment that prevents disability in RA must be started in an early manner, before the development of complications and, ideally, with a minimum possibility of therapeutic failure. As yet, there are no clinical or laboratory criteria to identify those patients with a higher probability of responding to particular types of therapy, delaying control of RA ad affecting the prevention of incapacity. Research into gene diversity through single-nucleotide polymorphisms (SNPs) by means of microarray systems, allows the detailed analysis of gene factors associated to a given disease. SNPs have been recently applied to the study of RA, where the major polymorphisms associated to RA occur primarily in genes that code for proteins related to the initiation of an immune response and/or the control of cellular activity in the immune system, in addition to genes related to tissue repair. The specific meaning of these findings is in its initial stages of research. On the other hand, proteomics relate to the analysis of protein expression profiles at multiple levels. Both types of studies will contribute to the knowledge of patterns of gene expression in RA compared to the general population, and will allow an understanding of the pathogenesis of RA. Moreover, proteomic and genomic profiles can be employed to designs probes that identify individuals with the risk of developing RA, individually predict the response to different therapeutic modalities (pharmacogenomics) and for the follow-up of the biologic response to therapy.