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CYP3A4 Expression in Breast Cancer and its Association with Risk Factors in Mexican Women
Floriano-Sanchez, Esau,Rodriguez, Noemi Cardenas,Bandala, Cindy,Coballase-Urrutia, Elvia,Lopez-Cruz, Jaime Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8
Background: In Mexico, breast cancer (BCa) is the leading type of cancer in women. Cytochrome P450 (CYP450) is a superfamily of major oxidative enzymes that metabolize carcinogens and many antineoplastic drugs. In addition, these enzymes have influence on tumor development and tumor response to therapy. In this report, we analyzed the protein expression in patients with BCa and in healthy women. Links with some clinic-pathological characteristic were also assessed. Materials and Methods: Immunohistochemical analyses were conducted on 48 sets of human breast tumors and normal breast tissues enrolled in Hospital Militar de Especialidades de la Mujer y Neonatologia and Hospital Central Militar, respectively, during the time period from 2010 to 2011. Informed consent was obtained from all participants. Statistical analysis was performed using ${\chi}^2$ or Fisher exact tests to estimate associations and the Mann Whitney U test for comparison of group means. Results: We found a significant CYP3A4 overexpression in BCa stroma and gland regions in comparison with healthy tissue. A significant association between protein expression with smoking, alcoholism and hormonal contraceptives use was also observed. Additionally, we observed estrogen receptor (ER) and progesterone receptor (PR) positive association in BCa. Conclusions: We suggest that CYP3A4 expression promotes BCa development and can be used in the prediction of tumor response to different treatments. One therapeutic approach may thus be to block CYP3A4 function.
RNA Expression of Cytochrome P450 in Mexican Women with Breast Cancer
Bandala, Cindy,Floriano-Sanchez, E.,Cardenas-Rodriguez, N.,Lopez-Cruz, J.,Lara-Padilla, E. Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6
Involvement of cytochrome P450 genes (CYPs) in breast cancer (BCa) may differ between populations, with expression patterns affected by tumorigenesis. This may have an important role in the metabolism of anticancer drugs and in the progression of cancer. The aim of this study was to determine the mRNA expression patterns of four cytochrome P450 genes (CYP2W1, 3A5, 4F11 and 8A1) in Mexican women with breast cancer. Real-time PCR analyses were conducted on 32 sets of human breast tumors and adjacent non-tumor tissues, as well as 20 normal breast tissues. Expression levels were tested for association with clinical and pathological data of patients. We found higher gene expression of CYP2W1, CYP3A5, CYP4F11 in BCa than in adjacent tissues and only low in normal mammary glands in our Mexican population while CYP8A1 was only expressed in BCa and adjacent tissues. We found that Ki67 protein expression was associated with clinicopathological features as well as with CYP2W1, CYP4F11 and CYP8A1 but not with CYP3A5. The results indicated that breast cancer tissues may be better able to metabolize carcinogens and other xenobiotics to active species than normal or adjacent non-tumor tissues.
Gene Expression of CYP1A1 and its Possible Clinical Application in Thyroid Cancer Cases
Gallegos-Vargas, JA,Sanchez-Roldan, J,Ronquillo-Sanchez, MD,Carmona-Aparicio, L,Floriano-Sanchez, E,Cardenas-Rodriguez, N Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.7
Background: Thyroid cancer is the most common endocrine malignancy, and exact causes remain unknown. The role of CYP450 1A1 (CYP1A1) in cancer initiation and progression has been investigated. The aim of this work was to analyze, for the first time, CYP1A1 gene expression and its relationship with several clinicopathological factors in Mexican patients diagnosed with thyroid cancer. Materials and Methods: Real-time PCR analysis was conducted on 32 sets of thyroid tumors and benign pathologies. Expression levels were tested for correlations with clinical and pathological data. All statistical analysis were performed using GraphPad Prism version 3.0 software. Results: We found that female gender was associated with thyroid cancer risk (P<0.05). A positive relationship was identified between CYP1A1 mRNA levels and the presence of chronic disease, alcohol use, tumor size, metastasis and an advanced clinical stage (P<0.05). Conclusions: The results suggest that CYP1A1 gene expression could be used as a marker for thyroid cancer.
Leon-Hernandez, Saul Renan,Padilla, Eleazar Lara,Algara, Alfredo Cortes,Rodriguez, Noemi Cardenas,Sanchez, Esau Floriano,Cruz, Jaime Lopez,Barradas, Cesar Miguel Mejia,Bandala, Cindy Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14
Background: An association between alcohol/tobacco use and risk of metastasis in breast cancer has been clearly shown. Materials and Methods: The present study explored, in 48 samples of tissue from mammary ductal carcinoma (taken from Mexican women with an average age of $58.2{\pm}10.9$ years), the association of risk of metastasis with the status of hormonal receptors and the c-erbB2 protein (by immunohistochemistry) as well as clinical, histopathological and sociodemographic factors. Results: Of 48 patients, 41.6% (20/48) presented with metastasis, 43.8% were positive for the estrogen receptor (RE+), 31.3% for the progesterone receptor (RP+) and 47.7% for c-erbB2 (c-erbB2+). The following combinations were found: RE+/RP+/c-erbB2+ 8.3%, RE+/RP+ 22.9%, RE+/RP- 20.8%, RE-/RP+ 8.3%, RE-/RP-/c-erbB2- 22.9% and RE-/RP- 47.8%. There were 12 patients who used alcohol/tobacco, of which 91.6% did not present metastasis and 81.9% were RE-/RP-. Compared to the RE-/RP-/c-erbB2+, the RE+/RP+/c-erbB2+ group had a 15-fold greater risk for metastasis (95%CI, 0.9-228.8, p=0.05). The carriers of the double negative hormonal receptors had a 4.7 fold greater probability of being (or having been) smokers or drinkers (95%CI, 1.0-20.4, p = 0.03). Conclusions: There was a clear protective effect of using alcohol and/or tobacco, in the cases included in the present study of mammary ductal carcinoma, associated with double negative hormonal receptors. However, this association could be due to a protective factor not measured (Neyman bias) or to a bias inherent in the rate of hospitalization (Berkson fallacy). This question should be explored in a broad prospective longitudinal study.
Cardenas-Rodriguez, N.,Lara-Padilla, E.,Bandala, C.,Lopez-Cruz, J.,Uscanga-Carmona, C.,Lucio-Monter, P.F.,Floriano-Sanchez, E. Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3
Breast cancer (BCa) is the leading type of cancer in Mexican women. Genetic factors, such as single nucleotide polymorphisms (SNP) of P450 system, have been reported in BCa. In this report, and for the first time in the literature, we analyzed the rs3735684 (7021 G>A), rs11553651 (15016 G>T) and rs56195291 (60020 C>G) polymorphisms in the CYP2W1, 4F11 and 8A1 genes in patients with BCa and in healthy Mexican women to identify a potential association between these polymorphisms and BCa risk. Patients and controls were used for polymorphism analysis using an allelic discrimination assay with TaqMan probes and confirmed by DNA sequencing. Links with clinic-pathological characteristics were also analyzed. Statistical analysis was performed using the standard ${\chi}^2$ or Fisher exact test statistic. No significant differences were observed in the distributions of CYP2W1 (OR 8.6, 95%CI 0.43-172.5 P>0.05; OR 2.0, 95%CI 0.76-5.4, P>0.05) and CYP4F11 (OR 0.3, 95%CI 0.01-8.4 P>0.05) genotypes between the patients and controls. Only the CYP8A1 CC genotype was detected in patients with BCa and the controls. All polymorphism frequencies were in Hardy-Weinberg Equilibrium (HWE) in the controls (P>0.05). We found a significant association between BCa risk and smoking, use of oral contraceptives or hormonal replacement therapy (HRT), obesity, hyperglycemia, chronic diseases, family history of cancer and menopausal status in the population studied (P<0.05). Tobacco, oral contraceptive or HRT, chronic diseases and obesity or overweight were strongly associated with almost eight, thirty-five, nine and five-fold increased risk for BCa. Tobaco, obesity and hyperglycemia significantly increased the risk of BCa in the patients carrying variant genotypes of CYP2W1 (P<0.05). These results indicate that the CYP2W1 rs3735684, CYP4F11 rs11553651 and CYP8A1 rs56195291 SNPs are not a key risk factor for BCa in Mexican women. This study did not detect an association between the CYP2W1, 4F11 and 8A1 genes polymorphisms and BCa risk in a Mexican population. However, some clinico-pathological risk factors interact with CYP2W1 genotypes and modifies susceptibility to BCa.
Bandala, Cindy,De la Garza-Montano, Paloma,Cortes-Algara, Alfredo,Cruz-Lopez, Jaime,Dominguez-Rubio, Rene,Gonzalez-Lopez, Nelly Judith,Cardenas-Rodriguez, Noemi,Alfaro-Rodriguez, A,Salcedo, M,Floriano Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.18
Background: Breast cancer (BCa) is the most common malignancy in Mexican women. A set of histopathological markers has been established to guide BCa diagnosis, prognosis and treatment. Nevertheless, in only a few Mexican health services, such as that of the Secretariat of National Defense (SEDENA for its acronym in Spanish), are these markers commonly employed for assessing BCa. The aim of this study was to explore the association of Ki67, TP53, HER2/neu, estrogenic receptors (ERs) and progesterone receptors (PRs) with BCa risk factors. Materials and Methods: Clinical histories provided background patient information. Immunohistochemical (IHC) analysis was conducted on 48 tissue samples from women diagnosed with BCa and treated with radical mastectomy. The Chi square test or Fisher exact test together with the Pearson and Spearman correlation were applied. Results: On average, patients were $58{\pm}10.4$ years old. It was most common to find invasive ductal carcinoma (95.8%), histological grade 3 (45.8%), with a poor Nottingham Prognostic Index (NPI; 80.4%). ERs and PRs were associated with smoking and alcohol consumption, metastasis at diagnosis and Ki67 expression (p<0.05). PR+ was also related to urea and ER+ (p<0.05). Ki67 was associated with TP53 and elevated triglycerides (p<0.05), and HER2/neu with ER+, the number of pregnancies and tumor size (p<0.05). TP53 was also associated with a poor NPI (p<0.05) and CD34 with smoking (p<0.05). The triple negative status (ER-/PR-/HER2/neu-) was related to smoking, alcohol consumption, exposure to biomass, number of pregnancies, metastasis and a poor NPI (p<0.05). Moreover, the luminal B subty was associated with histological type (p=0.007), tumor size (p=0.03) and high cholesterol (p=0.02). Conclusions: Ki67, TP53, HER2/neu, ER and PR proved to be related to several clinical and pathological factors. Hence, it is crucial to determine this IHC profile in women at risk for BCa. Certain associations require further study to understand physiological/biochemical/molecular processes.
da Silva Emmanuel João Nogueira Leal,de Moura Sara Gomes,de Lima Carolina Oliveira,Barbosa Ana Flávia Almeida,Misael Waleska Florentino,Lacerda Mariane Floriano Lopes Santos,Sassone Luciana Moura 대한치과보존학회 2021 Restorative Dentistry & Endodontics Vol.46 No.2
Objectives: The aim of this study was to evaluate the shaping ability of the TruShape and Reciproc Blue systems and the apical extrusion of debris after root canal instrumentation. The ProTaper Universal system was used as a reference for comparison. Materials and Methods: Thirty-three mandibular premolars with a single canal were scanned using micro-computed tomography and were matched into 3 groups (n = 11) according to the instrumentation system: TruShape, Reciproc Blue and ProTaper Universal. The teeth were accessed and mounted in an apparatus with agarose gel, which simulated apical resistance provided by the periapical tissue and enabled the collection of apically extruded debris. During root canal preparation, 2.5% sodium hypochlorite was used as an irrigant. The samples were scanned again after instrumentation. The percentage of unprepared area, removed dentin, and volume of apically extruded debris were analyzed. The data were analyzed using 1-way analysis of variance and the Tukey test for multiple comparisons at a 5% significance level. Results: No significant differences in the percentage of unprepared area were observed among the systems (p > 0.05). ProTaper Universal presented a higher percentage of dentin removal than the TruShape and Reciproc Blue systems (p < 0.05). The systems produced similar volumes of apically extruded debris (p > 0.05). Conclusions: All systems caused apically extruded debris, without any significant differences among them. TruShape, Reciproc Blue, and ProTaper Universal presented similar percentages of unprepared area after root canal instrumentation; however, ProTaper Universal was associated with higher dentin removal than the other systems.