Neural Transdifferentiation: MAPTau Gene Expression in Breast Cancer Cells

Lara-Padilla, E,Miliar-Garcia, A,Gomez-Lopez, M,Romero-Morelos, P,Bazan-Mendez, CI,Alfaro-Rodriguez, A,Anaya-Ruiz, M,Callender, K,Carlos, A,Bandala, C Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

Background: In tumor cells, aberrant differentiation programs have been described. Several neuronal proteins have been found associated with morphological neuronal-glial changes in breast cancer (BCa). These neuronal proteins have been related to mechanisms that are involved in carcinogenesis; however, this regulation is not well understood. Microtubule-associated protein-tau (MAP-Tau) has been describing in BCa but not its variants. This finding could partly explain the neuronal-glial morphology of BCa cells. Our aim was to determine mRNA expression of MAP-tau variants 2, 4 and 6 in breast cancer cell lines. Materials and Methods: Cultured cell lines MCF-10A, MDA-MB-231, SKBR3 and T47D were observed under phase-contrast microscopy for neural morphology and analyzed for gene expression of MAP-Tau transcript variants 2, 4 and 6 by real-time PCR. Results: Regarding morphology like neural/glial cells, T47D line shown more cells with these features than MDA-MB-231 and SKBR. In another hand, we found much greater mRNA expression of MAP-Tau transcript variants 2, and to a lesser extent 4 and 6, in T47D cells than the other lines. In conclusion, regulation of MAP-Tau could bring about changes in cytoskeleton, cell morphology and motility; these findings cast further light on neuronal transdifferentiation in BCa.

CYP2W1, CYP4F11 and CYP8A1 Polymorphisms and Interaction of CYP2W1 Genotypes with Risk Factors in Mexican Women with Breast Cancer

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.

Relation of Alcohol/Tobacco use with Metastasis, Hormonal (Estrogen and Progesterone) Receptor Status and c-erbB2 Protein in Mammary Ductal Carcinoma

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.

Effect of Botulinum Toxin A on Proliferation and Apoptosis in the T47D Breast Cancer Cell Line

Bandala, Cindy,Perez-Santos, Jose Luis Martin,Lara-Padilla, Eleazar,Delgado Lopez, Ma. Guadalupe,Anaya-Ruiz, Maricruz Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

The present study was performed to assess the activity of the botulinum toxin A on breast cancer cells. The T47D cell line was exposed to diverse concentrations of the botulinum toxin A and cell viability and apoptosis were estimated using MTT and propidium iodine/annexin V methods, respectively. Botulinum toxin A exerted greater cytotoxic activity in T47D cells in comparison with MCF10A normal cells; this appeared to be via apoptotic processes caspase-3 and -7. In conclusion, botulinum toxin A induces caspase-3 and -7 dependent apoptotic processes in the T47D breast cancer cell line.

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.

Prospective study analyzing risk factors and characteristics of healthcare-associated infections in a Urology ward

José Medina-Polo,Raquel Sopeña-Sutil,Raúl Benítez-Sala,Alba Lara-Isla,Manuel Alonso-Isa,Javier Gil-Moradillo,Juan Justo-Quintas,Esther García-Rojo,Daniel Antonio González-Padilla,Juan Bautista Passas- 대한비뇨의학회 2017 Investigative and Clinical Urology Vol.58 No.1

Purpose: Healthcare-associated infections (HAIs) in urological patients have special features due to specific risk factors. Our objective was to evaluate the characteristics and risk factors for HAIs in patients hospitalized in a Urology ward. Materials and Methods: We evaluated prospectively, from 2012 to 2015, the incidence, types and risk factor for HAIs, microbiological and resistance patterns. Results: The incidence of HAIs was 6.3%. The most common types were urinary infections (70.5%) and surgical site infections (22.1%). Univariate analysis showed an increased risk of HAIs among patients with American Society of Anesthesiologists physical status classification system III–IV (odds ratio [OR], 1.39; p<0.001), immunosuppression (OR, 1.80; p=0.013), previous urinary infection (OR, 4.46; p<0,001), and urinary catheter before admission (OR, 1.74; p<0.001). The surgical procedures with the highest incidence of HAIs were radical cystectomy (54.2%) and renal surgery (8.7%). The most frequently isolated microorganisms were Escherichia coli (25.1%), Enterococcus spp. (17.5%), Klebsiella spp. (13.5%) and Pseudomonas aeruginosa (12.3%). Enterococcus sp was the most common microorganism after radical cystectomy and in surgical site infections, E. coli showed resistance rates of 53.5% for fluoroquinolones, 9.3% for amikacin. The percentage of extended-spectrum betalactamase producing E. coli was 24.7%. Klebsiella spp. showed resistance rates of 47.8% for fluoroquinolones, 7.1% for amikacin and 4.3% for carbapenems. Enterococcus spp showed resistance rates of 1.7% for vancomycin and; P. aeruginosa of 33.3% for carbapenems and 26.2% for amikacin. Conclusions: Comorbidities, previous urinary infections, and urinary catheter are risk factors for HAIs. The microorganisms most commonly isolated were E. coli, Enterococcus and P. aeruginosa. Prospective monitoring may decrease the incidence of infections.

Synaptic Vesicle Protein 2 (SV2) Isoforms

Bandala, Cindy,Miliar-Garcia, A.,Mejia-Barradas, C.M.,Anaya-Ruiz, M.,Luna-Arias, J.P.,Bazan-Mendez, C.I.,Gomez-Lopez, M.,Juarez-Mendez, S.,Lara-Padilla, E. Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

New molecular markers of cancer had emerged with novel applications in cancer prevention and therapeutics, including for breast cancer of unknown causes, which has a high impact on the health of women worldwide. The purpose of this research was to detemine protein and mRNA expression of synaptic vesicle 2 (SV2) isoforms A, B and C in breast cancer cell lines. Cultured cell lines MDA-MB-231, SKBR3, T47D were lysed and their protein and mRNA expression analyzed by real-time PCR and western blot technique, respectively. SV2A, B proteins were identified in non-tumor (MCF-10A) and tumor cell lines (MDA-MB-231 and T47D) while SV2C only was found in the T47D cell line. Furthermore, the genomic expression was consistent with protein expression for a such cell line, but in MDA-MB-231 there was no SV2B genomic expression, and the SV2C mRNA and protein were not found in the non tumoral cell line. These findings suggest a possible cellular transdifferentiation to neural character in breast cancer, of possible relevance to cancer development, and point to possible use of SV2 as molecular marker and a vehicle for cancer treatment with botulinum toxin.