Association of the rs1966265 and rs351855 FGFR4 Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico.

The aim of this study was to associate FGFR4 rs1966265 and rs351855 variants with colorectal cancer (CRC) in a Mexican population and to perform in silico analysis. Genomic DNA from 412 healthy individuals and 475 CRC patients was analyzed. In silico analysis was performed using the PolyPhen-V2, GEPIA, GTEx, and Cytoscape platforms. The GA genotype dominant model (GAAA) of rs1966265 and the AA genotype dominant and recessive models of rs351855 were identified as CRC risk factors (p < 0.05). CRC patients aged ≥ 50 years at diagnosis who consumed alcohol had a higher incidence of the rs351855 GA genotype than the control group (p < 0.05). Associations were observed between the rs1966265 GA genotype and patients with rectal cancer and stage III-IV disease. The rs351855 AA genotype was a risk factor for partial chemotherapy response, and the GA + AA genotype for age ≥ 50 years at diagnosis and rectal cancer was associated with a partial response to chemotherapy (p < 0.05). The AA haplotype was associated with increased susceptibility to CRC. In silico analysis indicated that the rs351855 variant is likely pathogenic (score = 0.998). Genotypic expression analysis in blood samples showed statistically significant differences (p < 0.05). EFNA4, SLC3A2, and HNF1A share signaling pathways with FGFR4. Therefore, rs1966265 and rs351855 may be potential CRC risk factors.

Association of the rs8720 and rs12587 KRAS Gene Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico.

Colorectal cancer (CRC) is a major global health challenge and one of the top 10 cancers in Mexico. Lifestyle and genetic factors influence CRC development, prognosis, and therapeutic response; identifying risk factors, such as the genes involved, is critical to understanding its behavior, mechanisms, and prognosis. The association between KRAS gene variants (rs8720 and rs12587) and CRC in the Mexican population was analyzed. We performed in silico analysis and analyzed 310 healthy individuals and 385 CRC patients using TaqMan assays and real-time PCR. The CC and GG genotypes of rs8720 and rs12587 were identified as CRC risk factors (p < 0.05). The CC and TC genotypes of the rs8720 were associated with rectal cancer, age over 50 years, moderately differentiated histology, and advanced cancer stage. TG and GG genotypes of the rs12587 variant were a risk factor in the CRC group, in patients with stage I-II, males, and stage III-IV non-chemotherapy response. The TG haplotype is protected against CRC. The combined CCGG genotype was linked to CRC risk. In silico analysis revealed that the rs12587 and rs8720 variants could influence KRAS gene regulation via miRNAs. In conclusion, rs8720 and rs12587 variants of the KRAS gene were associated with CRC risk and could influence KRAS regulation via miRNAs.

GC/MS Analysis, Antioxidant Activity, and Antimicrobial Effect of Pelargonium peltatum (Geraniaceae).

In recent years, the increase in antibiotic resistance demands searching for new compounds with antimicrobial activity. Phytochemicals found in plants offer an alternative to this problem. The genus Pelargonium contains several species; some have commercial use in traditional medicine such as P. sinoides, and others such as P. peltatum are little studied but have promising potential for various applications such as phytopharmaceuticals. In this work, we characterized the freeze-dried extracts (FDEs) of five tissues (root, stem, leaf, and two types of flowers) and the ethyl acetate fractions from leaf (Lf-EtOAc) and flower (Fwr-EtOAc) of P. peltatum through the analysis by thin-layer chromatography (T.L.C.), gas chromatography coupled to mass spectrometry (GC-MS), phytochemicals quantification, antioxidant capacity, and antimicrobial activity. After the first round of analysis, it was observed that the FDE-Leaf and FDE-Flower showed higher antioxidant and antimicrobial activities compared to the other FDEs, for which FDE-Leaf and FDE-Flower were fractionated and analyzed in a second round. The antioxidant activity determined by ABTS showed that Lf-EtOAc and Fwr-EtOAc had the lowest IC50 values with 27.15 ± 1.04 and 28.11 ± 1.3 µg/mL, respectively. The content of total polyphenols was 264.57 ± 7.73 for Lf-EtOAc and 105.39 ± 4.04 mg G.A./g FDE for Fwr-EtOAc. Regarding the content of flavonoid, Lf-EtOAc and Fw-EtOAc had the highest concentration with 34.4 ± 1.06 and 29.45 ± 1.09 mg Q.E./g FDE. In addition, the minimum inhibitory concentration (M.I.C.) of antimicrobial activity was evaluated: Lf-EtOAc and Fwr-EtOAc were effective at 31.2 µg/mL for Staphylococcus aureus and 62.5 µg/mL for Salmonella enterica, while for the Enterococcus feacalis strain, Fwr-EtOAc presented 31.2 µg/mL of M.I.C. According to the GC-MS analysis, the main compounds were 1,2,3-Benzenetriol (Pyrogallol), with 77.38% of relative abundance in the Lf-EtOAc and 71.24% in the Fwr-EtOAc, followed by ethyl gallate (13.10%) in the Fwr-EtOAc and (Z)-9-Octadecenamide (13.63% and 6.75%) in both Lf-EtOAc and Fwr-EtOAc, respectively.

ESR2 gene variants (rs1256049, rs4986938, and rs1256030) and their association with breast cancer risk.

Background: Variants of the estrogen receptor b (ESR2) gene have been associated with different types of cancer. However, these associations have been inconsistent. We genotyped the ESR2 variants (rs1256049, rs4986938, and rs1256030) in breast cancer (BC) patients and in healthy women. Results: The variants rs1256049 and rs4986938 in the ESR2 gene were not associated with risk susceptibility in BC patients. However, the rs1256030 variant had an association as a risk factor for BC patients when compared with controls and BC patients for the TT genotype (odds ratio (OR) 1.86, 95% confidence intervals (CI) [1.05-3.28], p = 0.042). In addition, differences were observed in patients and controls carrying the TT genotype under 50 years of age (OR 1.85, 95% CI [1.05-3.27], p = 0.043). Thus, evident differences showed the rs1256030 variant in patients with TT, TC, and TC+TT genotypes with: (1) Stage IV (OR 1.60, 95% CI [1.06-2.54], p = 0.033), and (2) Luminal A (OR 1.60, 95% CI [0.47-0.21], p = 0.041), as well as in BC carriers of the TT genotype with indices of cellular proliferative (Ki-67) elevated (>20%) and overweight (OR 1.67, 95% CI [0.85-3.28], p = 0.041), respectively. In BC HER2 with lymph node metastasis, the TT genotype was a protective factor (OR 0.38, 95% CI [0.18-0.78], p = 0.005). The identification of haplotypes included two common GAT as risk factors (OR 3.1, 95% CI [1.31-7.72], p = 0.011) and GGC as a protective factor (OR 0.7, 95% CI [0.60-0.97], p = 0.034). The haplogenotype GGGATC was a risk factor (OR 2.5, 95% CI [1.28-5.0], p = 0.008). Conclusion: The variant rs1256030 (TT) of the ESR2 gene and haplotype GAT were associated with susceptibility to BC as risk factors in this sample from the Mexican population.

Protective effect of rs712 polymorphism in a let-7 microRNA-binding of KRAS gene in breast cancer of a Mexican population.

PURPOSE: The rs712 polymorphism in a let-7 microRNA-binding KRAS gene has been associated with different types of cancer, however these associations have been inconsistent. The purpose of this study was to determine the association between rs712 polymorphism in a let-7 microRNA-binding KRAS gene comparing breast cancer (BC) patients with healthy subjects from Mexican population. METHODS: The genotyping of the rs712 polymorphism was performed by polymerase chain reaction (PCR) in 437 BC patients and 414 healthy women. RESULTS: The observed frequencies of the rs712 polymorphism indicated an associated protective factor for BC in the dominant GT+TT model [odds ratio (OR) 0.70, 95% confidence interval (CI) 0.51-0.97, p=0.040). An association between genotype and BC patients was evident in chemotherapy response (allele GT, OR 0.032, 95% CI 0.002-0.505, p=0.014), partial chemotherapy response (genotype GT, OR 0.023, 95% CI 0.001-0.419, p=0.011), and gastric and hematological toxicity (genotype GT, OR 0.115, 95% CI 0.028-0.473, p=0.003), Luminal A BC patients with gastric and hematological toxicity (genotype TT, OR 0.236, 95% CI 0.069-0.805, p=0.021) and tobacco consumption (genotype TT, OR 0.283, 95% CI 0.001-0.802, p=0.037) and Luminal B with metastatic lymph node (genotype GT, OR 0.241, 95% CI 0.093-0.626, p=0.003). CONCLUSION: Polymorphism rs712 in KRAS gene was protective factor associated with susceptibility for BC in this sample from Mexican population.

Association of rs2234693 and rs9340799 polymorphisms of ESR1 gene in breast cancer of Mexican population.

PURPOSE: The rs2234693 and rs9340799 ESR1 polymorphisms have shown contradictory results in studies of breast cancer (BC). The purpose of this study was to determine the frequency and association of ESR1 polymorphisms (rs2234693 and rs9340799) in BC patients of Mexican population. METHODS: PCR was used to genotype rs2234693 and rs9340799 polymorphisms in the ESR1 gene in Mexican healthy subjects and breast cancer (BC) patients. RESULTS: The frequency of cases and control groups of rs2234693 and rs9340799 polymorphisms in the ESR1 was similar, and none has shown any association with increased BC risk (p>0.05), although the association between the haplogenotypes (rs2234693 and rs9340799 polymorphisms) and BC patients with miscarriages [CTAG variant, adjusted odds ratio (OR) 1.83 (95%CI 1.17-2.86);p=0.011] and tobacco consumption [CCGG variant, adjusted OR 1.88 (95%CI 1.11-3.19);p=0.018] was evident. Also, the homozygous genotype TT [rs2234693, OR 1.49 (95%CI 1.02-2.19);p=0.042] and GG [rs9340799, OR 2.85 (95%CI 1.144-7.10);p=0.024] showed marginal association with BC, indicating that these factors may contribute significantly to the susceptibility of risk to BC. The TA haplotype was more common in controls than in CG. BC patients with a frequency around 0.71 among study groups, but without significant difference (p>0.05). CONCLUSION: rs2234693 and rs9340799 polymorphisms in the ESR1 gene were not associated with susceptibility for BC. However, the haplogenotypes CTAG and CCGG of rs2234693 and rs9340799 polymorphisms could contribute significantly to the susceptibility of risk in BC positive at miscarriage and tobacco consumption in this sample population.

Identification and molecular characterization of the tubulin-podophyllotoxin-type lignans binding site on Giardia lamblia.

There are several drugs for the treatment of giardiasis; however, there is a tendency for patients to abandon treatment because of drug-related adverse effects, resulting in relapses, acquired resistance, and higher rates of treatment failure. Recently, we reported some podophyllotoxin-type lignans from Bursera fagaroides var. fagaroides showing antigiardial activity. In the present work, we demonstrated that 5'-desmethoxy-peltatin-A-methylether (5-DES), acetylpodophyllotoxin (APOD), and podophyllotoxin (POD) affect the distribution and staining pattern of microtubular structures on Giardia trophozoites. Virtual screening results revealed that the lignans act via binding in a hydrophobic pocket in the heterodimer interface of tubulin in Giardia. This study provides useful insight to understand the action mechanism of 5DES, APOD, and POD on Giardia lamblia. The optimization of these podophyllotoxin-type lignans will lead to promising candidates for antigiardial drugs.

Association of rs712 polymorphism in a let-7 microRNA-binding site of KRAS gene with colorectal cancer in a Mexican population.

OBJECTIVES: The rs712 polymorphism in a let-7 microRNA-binding site at KRAS gene has been associated with cancer. To examine its association with rs712 polymorphism, we analyzed Mexican individuals with colorectal cancer (CRC) and healthy subjects. MATERIALS AND METHODS: Genotyping of the rs712 polymorphism was performed by polymerase chain reaction in 281 controls and 336 CRC patients. RESULTS: The observed frequencies of rs712 polymorphism indicated an associated protective factor for CRC (P=0.032). An association between genotype and the disease was evident in: colon localization (allele T, odds ratio (OR) 3.82, 95% confidence Intervals (CI) 2.77-5.28, P=0.0001), node metastasis (genotype TT, OR 2.49, 95% CI 1.45-4.28, P=0.0009), poor differentiation (genotype GT, OR 2.35, 95% CI 1.35-4.1, P=0.0033), and poor chemotherapy response (genotype GT, OR 2.6, 95% CI 1.7-4.24, P=0.0001). CONCLUSION: Comparison of the data from patients with control group showed that polymorphism of rs712 in KRAS gene was protective factor, which was associated with susceptibility for CRC. However, the genotypes TT and GT of rs712 polymorphism in KRAS could contribute significantly to colon localization, node metastasis, poor differentiation and poor chemotherapy response in CRC patients in this sample population.

Association of the IL-10 gene rs1800872 (-592 C>A) polymorphism with breast cancer in a Mexican population.

PURPOSE: Interleukin 10 (IL-10) gene polymorphisms are associated with different types of cancer, but these associations are inconsistent. The purpose of this study was to determine the frequency and association of the rs1800872 IL-10 gene polymorphism in Mexican women with breast cancer (BC). METHODS: The rs1800872 polymorphism was genotyped in 368 BC patients and 320 control women using the polymerase chain reaction (PCR). RESULTS: The rs1800872 polymorphism was a risk factor for BC compared to controls and BC patients with genotypes CA (p=0.004) and AA, and in the recessive model (p=0.0002), dominant model (CA+AA; p=0.0001), and allele A ( p=0.0001). Additionally, differences were observed in BC patients with the CA and CAAA genotypes who had chemotherapy gastric and hematological toxicity (p=0.022) and tumor stage IV (p=0.013) as a risk factor. Genotypes were CA in breastfeeding (p=0.017), AA in gastric toxicity (p=0.048), and CAAA in tumor stage I-II (p=0.019) as protective risk factors. In BC carriers of: 1) CAAA genotype with tumor stage I-II and breast feeding (≥6 months), 2) CA genotype BC Luminal A with tumor stage I-II, 3) CA genotype BC Luminal B with breastfeeding (≥6 months), and 4) CAAA genotypes in BC HER2 with indices of cellular proliferation (Ki-67) that were elevated (≥20%), were considered to be protective factors in BC patients. CONCLUSION: The IL-10 gene rs1800872 polymorphism was associated with BC susceptibility in this sample from the Mexican population.

TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A gene mutation in Mexican colorectal cancer patients.

OBJECTIVE: To examine the association between TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A mutation by comparing healthy subjects with colorectal cancer (CRC) patients in the Mexican population. METHOD: Genotyping of the 2R/3R was performed by polymerase chain reaction (PCR) and [IVS]14+1G>A mutation by real-time PCR analysis. RESULTS: The observed frequencies of the TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD did not indicate an increased risk for CRC (p>0.05). However we observed an association of the 2R/2R (OR 3.08, 95% CI 1.66-6.08, p=0.0017) and heterozygous (OR 1.98, 95% CI 1.32-2.97, p=0.0012) genotypes as risk factors when comparing controls and CRC patients that were also tobacco consumers. An association between the genotype and the disease was evident. The distribution of the 2R/2R genotype and hematological toxicity (adjusted OR 2.26, 95% CI 1.54-4.45, p=0.0259), heterozygous (2R/3R) with tumor stage III-IV (OR 1.81, 95% CI 1.11-2.94, p=0.020) and 2R/2R-2R/3R in non-chemotherapy response CRC patients with hematological (OR 2.3, 95% CI 1.21-4.4, p=0.014) and gastric toxicities (OR 3.11, 95% CI 1.18-8.2, p=0.035) confirmed that this factor may significantly contribute to the CRC susceptibility. CONCLUSION: TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD was not associated with susceptibility to CRC. However, the 2R/2R and 2R/3R genotypes of TYMS polymorphism could significantly contribute to hematological and gastric toxicity in CRC patients in this sample population.

Association of the Del1518 Promoter (rs3730485) Polymorphism in the MDM2 Gene with Breast Cancer in a Mexican Population.

INTRODUCTION: The MDM2 gene plays an important role in tumorigenesis. The data on the Del1518 promoter polymorphism in the MDM2 gene have revealed associations with cancer. MATERIAL AND METHODS: We examined the role of the MDM2 Del1518 polymorphism through a comparison of the genotypes of 345 healthy Mexican women with those of 742 Mexican women with breast cancer (BC). RESULTS: The genotype frequencies of the MDM2 Del1518 polymorphism in controls and patients with BC were 64% and 55.5% for ins/ins, 32% and 31.5% for ins/del, and 4% and 13% for del/del, respectively. The obtained odds ratio (OR) was 3.26, with a 95% confidence interval (95% CI) of 1.86-5.72 and p=0.0001, for the del/del genotype. An association was evident when we examined the distribution of the del/del genotype in patients with elevated levels of transaminase SGPT (OR=2.268; 95% CI=1.40-3.65; p=0.0001). Additionally, we observed an association of the genotypes del/del - ins/del in menopausal patients with BC with the following characteristics: tobacco consumption (OR = 1.93, 95% CI = 1.07-3.4, p=0.025), pregnancy loss (OR=2.44, 95% CI=1.37-4.35, p=0.0024), obesity (I-IV) (OR=1.8, 95% CI=1.1-2.9, p= 0.018), and elevated serum glucose levels (OR=3.72, 95% CI=2.0-6.85, p=0.0001). CONCLUSIONS: The MDM2 Del1518 polymorphism was associated with BC susceptibility, particularly in menopausal patients with BC who reported tobacco consumption, pregnancy loss, obesity and high glucose levels in the analyzed Mexican population.

Antigiardial Activity of Podophyllotoxin-Type Lignans from Bursera fagaroides var. fagaroides.

Giardiasis, a diarrheal disease, is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; unfortunately, all of them have variable efficacies and adverse effects. Bursera fagaroides has been known for its anti-inflammatory and antidiarrheal properties in Mexican traditional medicine. We investigated the in vitro anti-giardial activities of four podophyllotoxin-type lignans from Bursera fagaroides var. fagaroides, namely, 5'-desmethoxy-ß-peltatin-A-methylether (5-DES), acetylpodophyllotoxin (APOD), burseranin (BUR), and podophyllotoxin (POD). All lignans affected the Giardia adhesion and electron microscopy images revealed morphological alterations in the caudal region, ventral disk, membrane, and flagella, to different extents. Only 5-DES, APOD, and POD caused growth inhibition. Using the Caco-2 human cell line as a model of the intestinal epithelium, we demonstrated that APOD displayed direct antigiardial killing activity and low toxicity on Caco-2 cells. This finding makes it an attractive potential starting point for new antigiardial drugs.

Association of the Alu insertion polymorphism in the progesterone receptor gene with breast cancer in a Mexican population.

INTRODUCTION: The progesterone receptor (PR) gene plays an important role in reproduction-related events. Data on polymorphisms in the PR gene have revealed associations with cancer, particularly for the Alu insertion polymorphism, which has been suggested to affect progesterone receptor function and contribute to tumor promotion in the mammary gland. MATERIAL AND METHODS: We examined the role of the Alu insertion polymorphism in the PR gene by comparing the genotypes of 209 healthy Mexican women with those of 481 Mexican women with breast cancer (BC). RESULTS: The genotype frequencies observed in the controls and BC patients were 0% and 4% for T2/T2 (Alu insertion), 16% and 21% for T1/T2, and 84% and 75% for T1/T1 (Alu deletion), respectively. The obtained odds ratio (OR) was 1.7, with a 95% confidence interval (95% CI) of 1.1-2.6, p = 0.009, for the T1/T2-T2/T2 genotypes. The association was also evident when the distributions of the T1/T2-T2/T2 genotypes in patients in the following categories were compared: obesity grade II (OR = 1.81, 95% CI: 1.03-3.18, p = 0.039) and the chemotherapy response (OR = 1.91, 95% CI: 1.27-3.067, p = 0.002). CONCLUSIONS: The T1/T2-T2/T2 genotypes of the Alu insertion polymorphism in the PR gene are associated with BC susceptibility in the analyzed Mexican population.

The association between the 844ins68 polymorphism in the CBS gene and breast cancer.

INTRODUCTION: The cystathionine beta synthase (CBS) gene plays an important role in homocysteine metabolism because it catalyzes the first step of the transsulfuration pathway, during which homocysteine is converted to cystathionine. Polymorphisms of CBS have been associated with cancer. MATERIAL AND METHODS: We examined the role of the 844ins68 polymorphism by comparing the genotypes of 371 healthy Mexican women with the genotypes of 323 Mexican women with breast cancer (BC). RESULTS: The observed genotype frequencies for controls and BC patients were 1% and 2% for Ins/Ins, 13% and 26% for W/Ins, and 86% and 72% for W/W, respectively. We found that the odds ratio (OR) was 2.2, with a 95% confidence interval (95% CI) of 1.5-3.3, p = 0.0001. The association was also evident when comparing the distribution of the W/Ins-Ins/Ins genotypes in patients in the following categories: 1) menopause and high γ-glutamyltransferase (GGT) levels (OR of 2.17, 95% CI: 1.17-4.26, p = 0.02), 2) chemotherapy response and high lactate dehydrogenase (LDH) levels (OR 2.2, 95% CI: 1.08-4.4, p = 0.027), 3) chemotherapy response and high GGT levels (OR 2.46, 95% CI: 1.2-4.8, p = 0.007), and 4) body mass index (BMI) and III-IV tumor stage (OR 3.2, 95% CI: 1.2-8.3, p = 0.013). CONCLUSIONS: We conclude that the genotypes W/Ins-Ins/Ins of the 844ins68 polymorphism in the CBS gene contribute significantly to BC susceptibility in the analyzed sample 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.

Effect of ditaxin and heteranthin and inhibitory effect of Ditaxis heterantha extract on L5178Y tumor development in mice.

Ditaxis heterantha seeds are used as spices for flavoring and coloring food. Two new apocarotenoids derived from the seeds, heteranthin and ditaxin, were evaluated for their in vitro cytotoxic effects in murine lymphoma cells lines. Bioabsorption in mice and preventive and antitumor effects of the apocarotenoids were determined. Ditaxin and heteranthin showed cytotoxic effects in vitro against murine malignant cells and normal splenocyte cells. The 50% inhibitory concentration (IC(50)) for ditaxin in splenocytes was 0.1825 mM; in L5178Y, the IC(50) was 0.1923 mM. The heteranthin IC(50) in splenocytes was 0.1325 mM; in L5178Y, the value was 0.3889 mM. The maximum ditaxin plasma concentration was found after 2 hours of administration (mean±standard deviation, 7.5±2.05 µg/mL). Oral administration of the D. heterantha extract (100 mg/kg per day) for 14 days after the L5178Y lymphoma cell implantation showed no significant effect compared with groups that were not pretreated. However, tumor inhibition in groups treated intraperitoneally before inoculation with the L5178Y cells showed a significant difference (P<.001) compared with the groups not pretreated.

[Frequency of TS1494del6 polymorphism in colorectal patients from west of Mexico]. / Frecuencia del polimorfismo TS 1494del6 en pacientes con cáncer colorrectal del occidente de México.

Thymidylate synthase (TYMS) converts dUMP to dTMP, the rate-limiting nucleotide in DNA synthesis. It is also the target for 5-flurouracil, the most common chemotherapy agent for treatment of colorectal cancer (CRC). We designed a case-control study to investigate the frequency of TS 1494del6 polymorphism in patients with CRC and controls from Mexican population. The study consists of 253 patients with CRC and 200 control subjects. Risk of CRC was estimated by use of Odds ratio (95% CI) analysis. The genotype 6bp-/6bp- in CRC patients was 18% (45/253) and in controls was 11% (22/200) with Odds ratio of 1.8 (1 - 4) with P = 0.059. When stratifying the training groups by age (< 50 years), male gender, stage III-IV and presence of metastasis, the genotype 6bp-/6bp- was as risk (p < 0.05). The genotype 6bp-/6bp- in the region untranslated 3' of TS gene, in the analyzed sample participates in important way in the development of CRC of the Mexican population.

Polyamines as biomarkers of the antitumoral activity of Bursera fagaroides

En células normales y tumorales las poliaminas (Pas) putresina (Pu), espermidina (Spd) y espermina (Spm) son requeridas en múltiples funciones fundamentales del ciclo celular. Altos niveles de Pas han sido reportados en varios tipos de cáncer, por lo que han sido propuestas como biomarcadores del desarrollo tumoral. En el presente trabajo se reporta su utilidad como biomarcadores de la evolución del linfoma murino L5178Y en diferentes fluidos, células y tejidos. Los hallazgos también fueron aplicados al seguimiento del efecto antitumoral de Bursera fagaroides, ya reportado previamente. Se utilizó cromatografía de intercambio iónico para determinar los niveles de Pas en orina, células peritoneales linfocitos circulantes, esplenocitos, mesotelio e hígado de ratones BALB/c a los 10, 17 y 24 días de evolución del tumor y de ratones tratados con el exacto hidroalcohólico de la corteza de B. fagaroides administrado por vía oral o intaperitonealmente (i.p) los niveles urinarios de Spd no fueron detectables, mientras que el incremento de Pu en orina es el mejor biomarcador del crecimiento del linfoma. Además los niveles urinarios de Pu disminuyeron significativamente en ratones tratados intraperitonealmente con B. fagoroides, lo cual refuerza resultados anteriores. En este modelo la variación de los niveles urinarios de Pu es un biomarcador efectivo del desarrollo neoplástico, dado que permite seguir la evolución del linfoma L5178Y. Además, proporciona una herramienta para estudiar in vivo, el efecto antitumoral de B. fagaroides y de otros fármacos.

Dysregulation of the Th1/Th2 cytokine profile is associated with immunosuppression induced by hypothalamic-pituitary-adrenal axis activation in mice.

Hypothalamic-pituitary-adrenal (HPA) axis activation-induced immunosuppression is associated with increased concentration of circulating corticosterone and impaired cellular immune responses. The purpose of this study was to investigate the effect of chronic HPA axis activation on the cellular immune response, Th1/Th2 cytokine profile, and concentration of corticosterone. Mice were divided into two groups: a control group comprised of healthy, untreated mice that received no stress, and an HPA axis-activated group that received stress through electric shock (ES). The delayed-type hypersensitivity reaction to dinitrofluorobenzene, splenocyte proliferative response to mitogens Concanavalin A and lipopolysaccharide, Th1 and Th2 profile, and TGF-beta1 production were measured in plasma and in culture supernatants. The corticosterone concentration was also measured in plasma. In the ES group, elevated plasma corticosterone concentration was associated with immunosuppression and a significant decrease in plasma concentrations of IL-2, IL-4, and TGF-beta1. In vitro IL-2 production in response to Con A was significantly lower in the ES group than in the control group. TGF-beta1 production in nonstimulated and stimulated cultures in response to either mitogen was significantly lower in the ES group than in the control group. Plasma concentrations of IFN-gamma and IL-10 did not differ significantly between groups. The concentrations of IFN-gamma, IL-4, and IL-10 in the supernatants of splenocytes stimulated with either mitogen and IL-4 production by nonstimulated cells were significantly higher in the ES group than in the control group. These results suggest that corticosterone mediates the immunosuppression induced by HPA axis activation, and induces dysregulation of the Th1/Th2 cytokine profile.