Increased homocysteine plasma levels in breast cancer patients of a Mexican population

Aim: Hyperhomocysteinemia has been associated with different pathologies, including cardiovascular diseases, hypertension, diabetes, and breast cancer (BC). To examine the differences in total homocysteine (tHcy) plasma levels, we compared healthy women to BC patients from a Mexican population. Materials and Methods: The tHcy plasma levels were measured using high-performance liquid chromatography with a fluorescence detector in 89 female controls and 261 BC patients. Results: The observed plasma tHcy levels were significantly higher among the BC patients (11.1019 ± 5.9161 µmol/l) compared to the controls (9.1046 ± 1.3213 µmol/l) (p = 0.002), and these differences were evident when stratified by age (≥ 50 years old), menopause status, overweight and obesity, miscarriages, node metastases, progression, subtype classification (luminal, Her2 and triple negative) and nonresponse to chemotherapy. Conclusions: The tHcy plasma levels could be a good marker for the progression and chemosensitivity of BC in the analyzed sample from a Mexican population. Key Words: plasma levels, homocysteine, HPLC, breast cancer, Mexican population

Polyamines as biomarkers of the antitumoral activity of Bursera fagaroides

In normal and tumoral cells, the polyamines (PAs) putrescine (Pu), spermidine (Spd) and spermine (Spm) are required in multiple fundamental cell cycle functions. High levels of PAs have been reported in many types of cancer, which is why they were proposed as biomarkers of cancer growth. In the present work, their utility as biomarkers of the evolution of the murine L5178Y lymphoma is reported in different body fluids, cells and tissues. Findings were also applied to the follow-up of the previously reported anti-tumor effect of Bursera fagaroides. Cation exchange chromatography was used to determine the PAs levels in urine, peritoneal cells, circulating lymphocytes, spleenocytes, mesothelium and liver of BALB/c mice at days 10, 17 and 24 of tumoral evolution. PAs levels were also measured in urine from mice treated, intraperitoneally or orally, with the hydroalcoholic extract of the bark of B. fagaroides. Spd and Spm urinary levels were not detectable, while Pu increase in urine is the best biomarker to detect lymphoma growth. Furthermore, Pu urinary levels decreased significantly in mice treated intraperitoneally with B. fagaroides. In this model, variations of the Pu urinary level is an effective biomarker of neoplastic growth as it allows to follow the evolution of L5178Y lymphoma, providing an in vivo assay for the antitumoral effect of B. fagaroides and other drugs

Bioactive extracts of Citrus aurantifolia swingle seeds obtained by supercritical CO<inf>2</inf> and organic solvents comparing its cytotoxic activity against L5178Y leukemia lymphoblasts

Citrus seeds are sources of secondary metabolites including limonoids, which have demonstrated cytotoxic activity. There are several reports of limonoid extraction methods. However, there are no studies that compare extraction methods and their optimization. The aim of this work was to evaluate two extraction methods for obtaining limonoid extracts from Citrus aurantifolia seeds and to evaluate their cytotoxic activity against L5178Y lymphoma cells. In solvent extraction, we evaluated two factors: time and solvent type, while for supercritical extraction, pressure and temperature were evaluated. Cytotoxic activities of extracts were carried out in vitro. Time and solvent did not affect cytotoxic activity, but they did affect limonin content and yield extraction. Supercritical extraction pressure did not affect the limonin yield, but latter was affected by temperature process. There was no difference in cytotoxic activity between extracts, showing an IC50 of 8.5 ?g/mL for supercritical CO2 and of 9 ?g/mL for solvent extracts. Zapotitlán 2015, Elsevier B.V. All rights reserved

Communication Power

El objetivo del presente trabajo fue estudiar el efecto del extracto acuoso de Bursera fagaroides y Difluorometilornitina (DFMO), aplicados de forma individual y combinados, sobre los tejidos sanos en el modelo de linfoma murino L5178Y y específicamente sobre el metabolismo de las poliaminas (PAs), Putresina (Pu), Espermidina (Spd) y Espermina (Spm). Mediante cromatografía de intercambio iónico se determinaron los niveles de Pu en orina como indicadores de la evolución del tumor, mientras por radioinmunoensayo se cuantificó la actividad de la ODC renal. Los resultados obtenidos sugieren que no se combine la ingestión de algún tipo de té o brebaje preparado con dicha planta cuando se administre DFMO, dado su efecto estimulador del desarrollo tumoral, contrario al efecto anticáncer del extracto hidroalcohólico de la misma planta

Communication Power

El objetivo del presente trabajo fue estudiar el efecto del extracto acuoso de Bursera fagaroides y Difluorometilornitina (DFMO), aplicados de forma individual y combinados, sobre los tejidos sanos en el modelo de linfoma murino L5178Y y específicamente sobre el metabolismo de las poliaminas (PAs), Putresina (Pu), Espermidina (Spd) y Espermina (Spm). Mediante cromatografía de intercambio iúnico se determinaron los niveles de Pu en orina como indicadores de la evolución del tumor, mientras por radioinmunoensayo se cuantificó la actividad de la ODC renal. Los resultados obtenidos sugieren que no se combine la ingestión de algún tipo de té o brebaje preparado con dicha planta cuando se administre DFMO, dado su efecto estimulador del desarrollo tumoral, contrario al efecto anticáncer del extracto hidroalcohólico de la misma planta

INCREASED HOMOCYSTEINE PLASMA LEVELS IN BREAST CANCER PATIENTS OF A MEXICAN POPULATION

Aim: Hyperhomocysteinemia has been associated with different pathologies, including cardiovascular diseases, hypertension, diabetes, and breast cancer (BC). To examine the differences in total homocysteine (tHcy) plasma levels, we compared healthy women to BC patients from a Mexican population. Materials and Methods: The tHcy plasma levels were measured using high-performance liquid chromatography with a fluorescence detector in 89 female controls and 261 BC patients. Results: The observed plasma tHcy levels were significantly higher among the BC patients (11.1019 ± 5.9161 µmol/l) compared to the controls (9.1046 ± 1.3213 µmol/l) (p = 0.002), and these differences were evident when stratified by age (≥ 50 years old), menopause status, overweight and obesity, miscarriages, node metastases, progression, subtype classification (luminal, Her2 and triple negative) and nonresponse to chemotherapy. Conclusions: The tHcy plasma levels could be a good marker for the progression and chemosensitivity of BC in the analyzed sample from a Mexican population. Key Words: plasma levels, homocysteine, HPLC, breast cancer, Mexican population

SOD1 gene variants rs4817415, rs2070424, and rs1041740 and their association with breast cancer risk

OBJECTIVE: The aim of this investigation was to determine the frequency and association of the variants rs4817415, rs2070424, and rs1041740 of the SOD1 gene in healthy women and breast cancer (BC) patients. PATIENTS AND METHODS: Genomic DNA samples from 146 healthy women and 130 patients with BC were analyzed. RESULTS: GG genotype (OR 2.54, 95% CI 1.31-4.91, p = 0.0073) and the G allele (OR 1.37, 95% CI 1.09-1.73, p = 0.007) of the rs2070424 variant and CC genotype (OR 1.67, 95% CI 1.04-0.2.70, p = 0.0444) and allele C (OR 1.58, 95% CI 1.09-2.29, p = 0.0183) of the rs1041740 variant of SOD1 gene were associated as risk factors for BC susceptibility relative to the control group. Study groups comparison of the stratification by menopausal status showed an association of susceptibility to BC risk with carriers of the GG genotype (OR 2.9, 95% CI 1.11-7.81, p = 0.042) of the rs2070424 variant and with the premenopausal status of the study group and the TT (OR 2.89, 95% CI 1.73-4.85, p = 0.001) genotype of the rs1041740 variant. Furthermore, differences were observed in the patients with BC who were carriers of the CC genotype of the rs4817415 variant with elevated Ki-67 (≥ 20%) and who presented lymph node metastasis and stage III-IV BC (p<0.05). Two common haplotypes were identified in the study groups: CAC (protective factor), and CGC (risk factor) (p<0.05). CONCLUSIONS: The rs2070424 and rs1041740 variants of the SOD1 gene and the CGC haplotype were associated as risk susceptibility factors of BC in this sample analyzed

Intron 4 VNTR (4a/b) polymorphism of the endothelial nitric oxide synthase gene is associated with breast cancer in Mexican women.

The endothelial nitric oxide synthase (eNOS) gene plays an important role in several biological functions. Polymorphisms of the eNOS gene have been associated with cancer. It has been suggested that the VNTR 4 a/b polymorphism may affect the expression of eNOS and contributes to tumor promotion in the mammary gland. We examined the role of the eNOS4 a/b polymorphism by comparing the genotypes of 281 healthy Mexican women with the genotypes of 429 Mexican women with breast cancer (BC). The observed genotype frequencies for control and BC patients were 0.6% and 0.7% for a/a (polymorphic); 87% and 77% for a/a (wild type); and 12% and 22% for a/b respectively. We found that the odds ratio (OR) was 1.9, with a 95% confidence interval (95%CI) of 1.29-2.95, P = 0.001 for genotypes a/a-a/b, b/c. The association was also evident when comparing the distribution of the a/a-a/b genotypes in patients with high levels of glutamate-oxaloacetate transaminase (SGOT) (OR, 1.93; 95% CI, 1.14-3.28; P = 0.015); undergoing menopause with high levels of SGOT (OR, 2.0; 95% CI, 1.1-3.84); and with high levels of glutamic-pyruvic transaminase (SGPT) (OR, 3.5; 95% CI, 1.56-8.22). The genotypes a/a-a/b are associated with BC susceptibility in the analyzed samples from the Mexican population

Intron 4 VNTR (4a/b) polymorphism of the endothelial nitric oxide synthase gene is associated with breast cancer in Mexican women.

The endothelial nitric oxide synthase (eNOS) gene plays an important role in several biological functions. Polymorphisms of the eNOS gene have been associated with cancer. It has been suggested that the VNTR 4 a/b polymorphism may affect the expression of eNOS and contributes to tumor promotion in the mammary gland. We examined the role of the eNOS4 a/b polymorphism by comparing the genotypes of 281 healthy Mexican women with the genotypes of 429 Mexican women with breast cancer (BC). The observed genotype frequencies for control and BC patients were 0.6% and 0.7% for a/a (polymorphic); 87% and 77% for a/a (wild type); and 12% and 22% for a/b respectively. We found that the odds ratio (OR) was 1.9, with a 95% confidence interval (95%CI) of 1.29-2.95, P = 0.001 for genotypes a/a-a/b, b/c. The association was also evident when comparing the distribution of the a/a-a/b genotypes in patients with high levels of glutamate-oxaloacetate transaminase (SGOT) (OR, 1.93; 95% CI, 1.14-3.28; P = 0.015); undergoing menopause with high levels of SGOT (OR, 2.0; 95% CI, 1.1-3.84); and with high levels of glutamic-pyruvic transaminase (SGPT) (OR, 3.5; 95% CI, 1.56-8.22). The genotypes a/a-a/b are associated with BC susceptibility in the analyzed samples from the Mexican population

Association of the tumor necrosis factor-alpha -308G>A polymorphism with breast cancer in Mexican women

The tumor necrosis factor-alpha (TNF-α) gene plays an important role in cell proliferation, differentiation, apoptosis, lipid metabolism, coagulation, insulin resistance, and endothelial function. Polymorphisms of TNF-α have been associated with cancer. We examined the role of the -308G>A polymorphism in this gene by comparing the genotypes of 294 healthy Mexican women with those of 465 Mexican women with breast cancer. The observed genotype frequencies for controls and breast cancer patients were 1 and 14% for AA, 13 and 21% for GA, and 86 and 65% for GG, respectively. We found that the odds ratio (OR) for AA genotype was 2.4, with a 95% confidence interval (95%CI) of 5.9-101.1 (P = 0.0001). The association was also evident when comparing the distribution of the AA-GA genotype in patients in the following categories: 1) premenopause and obesity I (OR = 3.5, 95%CI = 1.3-9.3, P = 0.008), 2) Her-2 neu and tumor stage I-II (OR = 2.5, 95%CI = 1.31-4.8, P = 0.004), 3) premenopause and tumor stage III-IV (OR = 1.7, 95%CI = 1.0-2.9, P = 0.034), 4) chemotherapy non-response and abnormal hematocrit (OR = 2.4, 95%CI = 1.2-4.8, P = 0.015), 5) body mass index and Her-2 neu and III-IV tumor stage (OR = 2.8, 95%CI = 1.2-6.6, P = 0.016), and 6) nodule metastasis and K-I67 (OR = 4.0, 95%CI = 1.01-15.7, P = 0.038). We concluded that the genotypes AA-GA of the -308G>A polymorphism in TNF-α significantly contribute to breast cancer susceptibility in the analyzed sample from the Mexican population. © FUNPEC-RP