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Unidad San Miguel Jagüeyes, Mexico

Gonzalez-Herrera A.L.,Laboratorio Of Oncologia Molecular | Salgado-Bernabe M.,Laboratorio Of Oncologia Molecular | Velazquez-Velazquez C.K.,Laboratorio Of Oncologia Molecular | Salcedo-Vargas M.,Laboratorio Of Oncologia Genomica | And 3 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2015

Background: Cervical cancer (CeCa) is the second most common cancer in women in developing countries, and human papilloma virus (HPV) is the primary etiological factor. Aberrant expression of HOX transcription factors has been observed in several types of cancer. To date, however, no reports exist on the expression of HOXB2 and HOXB13 proteins during neoplastic progression in CeCa and its correlation with HPV infection. Materials and Methods: Expression of HOXB2 and HOXB13 proteins was assessed in tissue microarrays from normal cervical epithelium, cervical intraepithelial neoplasias grade 1-3, and CeCa. HPV was detected by PCR and sequencing. Expression of HOX-positive cells was determined in each diagnostic group. Results: Percentage of HOXB2- and HOXB13-positive cells gradually increased from means of 10.9% and 16.7%, respectively, in samples from healthy women, to 75.2% and 88.6% in those from CeCa patients. Frequency of HPV infection also increased from 13% in healthy tissue samples to 92.3% in CeCa. Both HOXB2 and HOXB13 proteins were preferentially expressed in HPV+ samples. Conclusions: The present study represents the first report on the expression of both HOXB2 and HOXB13 proteins through cervix tumorigenesis, providing evidence that increased expression of such proteins is a common event during progression to CeCa.

Valdivia A.,Laboratorio Of Oncologia Genomica | Peralta R.,Laboratorio Of Oncologia Genomica | Matute-Gonzalez M.,Educacion Medica Continua | Cebada J.M.G.,Hospital de Gineco Obstetricia No. 3 | And 7 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2011

The metalloproteinases (MMP) 11 and 12 have been shown to be expressed in cervical cancer (CC). In order to extend our previous results, these MMPs were evaluated in cervical precursor lesions. One hundred seventeen cervical scrapes: thirty-six normal, thirty-six Low grade squamous lesions (LSIL), thirty-six High grade (HSIL), nine CC; and, also ninety-nine paraffin-embedded cervical lesions: fifteen normal cervices, thirty eight LSIL, sixteen HSIL, and five CC were collected. The samples were analyzed for relative expression by real time RT-PCR or immunohistochemistry assay. We were able to identify a relative increased expression of MMP11 in 75% and 78% from LSIL and HSIL samples, respectively. While MMP12 expression was 64% and 75% in LSIL and HSIL, respectively. Positive samples for MMP11 expression were also positive for MMP12 expression and also increased according to illness progression. In the tissues, MMP11 or MMP12 expression was observed in the cytoplasm of the neoplastic cells, while in the normal epithelium was absent. The reaction was always stronger for MMP12 than MMP11. MMP11 expression was present in 77% and 66% of LSIL and HSIL, while MMP12 expression was 73% and 68%. There was a relationship between MMP11 or MMP12 expression and HPV infection. Our data are showing a relationship between diagnostic of precursor lesions and the MMP11 and 12 expressions, suggesting that their expression could be an early event in the neoplastic lesions of the cervix and could have clinical significance.

Gonzalez-Yebra B.,University of Guanajuato | Peralta R.,University of Guanajuato | Peralta R.,Laboratorio Of Oncologia Genomica | Gonzalez A.L.,University of Guanajuato | And 3 more authors.
Diagnostic Pathology | Year: 2012

Background: Association between DNA alterations and clinical parameters as recurrence, survival or prognosis has been found in a variety of tumors. A clear association between Medullary Thyroid Carcinoma (MTC) and RET oncogene mutation has been accepted. Specifically M918T RET mutation represents the main genetic event in most cases of sporadic MTC (SMTC) and limited chromosomal alterations analyses have been performed.Methods: In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a primary tumor in a M918T RET mutation-positive SMTC patient and from its lymph node metastasis to investigate additional genetic alterations. We studied a patient with 15 years of follow-up and persistence of disease, confirmed by periodical elevated serum calcitonin (CT) levels.Results: Only 3 chromosomal imbalances were identified in the primary tumor, gain of 18p, and loss of 6p and 16p region, whereas 25 chromosomal imbalances were identified in the metastasis (9 gains and 16 losses).Conclusion: The chromosomal changes 6p-, 16p-, 18p + could determine in part the oncogenic phenotype in the primary M918T RET positive tumor and probably related to persistence of high serum CT levels in this patient. The additional chromosomal changes observed could be related to the metastasis phenotype. We suggest that some genes mapped at 6p, 16p and 18p chromosomal regions, could act as genes associated to cancer and could be related to persistent SMTC and good prognosis.Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1720753793691097. © 2012 González-Yebra et al.; licensee BioMed Central Ltd.

Peralta-Rodriguez R.,Laboratorio Of Oncologia Genomica | Romero-Morelos P.,Laboratorio Of Oncologia Genomica | Villegas-Ruiz V.,Laboratorio Of Oncologia Genomica | Mendoza-Rodriguez M.,Laboratorio Of Oncologia Genomica | And 4 more authors.
Infectious Agents and Cancer | Year: 2012

Background: Human Papillomavirus (HPV) in cervical epithelium has been identified as the main etiological factor in the developing of Cervical Cancer (CC), which has recently become a public health problem in Mexico. This finding has allowed for the development of vaccines that help prevent this infection. In the present study, we aimed to determine the prevalence and HPV type-distribution in Mexican women with CC, high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL), and Normal cytology (N) to estimate the impact of the HPV vaccines. Methods. The PubMed database was used to identify and review all articles that reported data on HPV prevalence in CC, precursor lesions, and normal cytology of Mexican women. Results: A total of 8,706 samples of the tissues of Mexican women were stratified according to diagnosis as follows: 499 for CC; 364 for HSIL; 1,425 for LSIL, and 6,418 for N. According to the results, the most prevalent genotypes are the following: HPV16 (63.1%), -18 (8.6%), -58, and -31 (5%) for CC; HPV-16 (28.3%), 58 (12.6%), 18 (7.4%), and 33 (6.5%) for HSIL; HPV-16 (13.1%), 33 (7.4%), 18 (4.2%), and 58 (2.6%) for LSIL, and HPV-16 (3.4%), 33 (2.1%), 18, and 58 (1.2%) for N. Conclusions: Taken together, genotypes 58 and 31 (10%) are more common than type 18 (8.6%) in CC. Therefore, the inclusion of these two genotypes in a second-generation vaccine would provide optimal prevention of CC in Mexico. © 2012 Peralta-Rodríguez et al.

Pacheco-Rivera R.A.,Laboratorio Of Diagnostico Molecular | Pacheco-Rivera R.A.,Laboratorio Of Oncologia Genomica | Hernandez-Zamora E.,Instituto Nacional Of Rehabilitacion | Gonzalez-Yebra B.,University of Guanajuato | And 5 more authors.
Clinical and Experimental Medicine | Year: 2011

The most important mutation associated with Multiple Endocrine Neoplasia type 2B (MEN 2B) is the change of thymine to cytosine in codon 918 of exon 16 in the RET oncogene (ATG → ACG). The aim of this work was to develop a single oligoarray by using tandem hybridization to detect the T918C/RET mutation for MEN 2B patients. Two genetically non-related families were studied; each family had a member affected by MEN2B. Both patients presented the T918C/RET mutation in a heterozygous fashion. None of the relatives was positive for this mutation; thus, these cases arose de novo. The proper mutation was confirmed by with different tools, PCR-Fok I endonuclease, direct sequencing, and also using our oligoarray. In this case, it is suitable to use a DNA target smaller than 150 bases with single- or doublestranded DNA and short probes of 7-mer. It was also possible to detect the mutation by employing different sources of DNA, fresh or paraffin-embedded tissues. Therefore, the present oligoarray can identify the most common M918T mutation of RET oncogene from a variety of DNA sources with good specificity and be a good alternative in the molecular diagnosis for MEN 2B cases. © Springer-Verlag 2011.

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