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1.
Int J Mol Sci ; 25(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38928478

RESUMO

Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of BRCA1 (BRCA1Δ9-12), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV BRCA1Δ9-12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT-qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9-12 alleles using nanopore long-sequencing. Using the Kruskal-Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous BRCA1 control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV BRCA1Δ9-12 and identifying which of them has developed cancer.


Assuntos
Alelos , Proteína BRCA1 , Síndrome Hereditária de Câncer de Mama e Ovário , Humanos , Proteína BRCA1/genética , Feminino , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Pessoa de Meia-Idade , Predisposição Genética para Doença , Adulto , Efeito Fundador , Éxons/genética , Neoplasias da Mama/genética , Heterozigoto , Mutação , México , Neoplasias Ovarianas/genética , Relevância Clínica
2.
J Neurooncol ; 161(1): 165-174, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36525166

RESUMO

PURPOSE: Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53. Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients. METHODS: We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT, MGMT and TP53, and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort). RESULTS: In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival. CONCLUSIONS: The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Feminino , Humanos , Masculino , Astrocitoma/patologia , Biomarcadores , Neoplasias Encefálicas/patologia , DNA/uso terapêutico , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Mutação , Prognóstico , Análise de Sequência de DNA , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genética
3.
Int J Mol Sci ; 23(19)2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36232851

RESUMO

Lynch syndrome (LS) is the main hereditary colorectal cancer syndrome. There have been few reports regarding the clinical and molecular characteristics of LS patients in Latin America; this is particularly true in the Mexican population, where no information is available. The present study aims to describe the clinical and molecular spectrum of variants in a cohort of patients diagnosed with LS in Mexico. We present a retrospective analysis of 412 patients with suspected LS, whose main site of cancer diagnosis was the colon (58.25%), followed by the endometrium (18.93%). Next-generation sequencing analysis, with an extensive multigene panel, showed that 27.1% (112/414) had a variant in one of the genes of the mismatch repair pathway (MMR); 30.4% (126/414) had a variant in non-MMR genes such as CHEK2, APC, MUTYH, BRCA1, and BRCA2; and 42.5% (176/414) had no genetic variants. Most of the variants were found in MLH1. Pathogenic variants (PVs) in MMR genes were identified in 65.7% (96/146) of the total PVs, and 34.24% (45/146) were in non-MMR genes. Molecular and clinical characterization of patients with LS in specific populations allowed personalized follow-up, with the option for targeted treatment with immune checkpoint inhibitors and the development of public health policies. Moreover, such characterization allows for family cascade testing and consequent prevention strategies.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Proteínas de Ligação a DNA/genética , Feminino , Mutação em Linhagem Germinativa , Humanos , Inibidores de Checkpoint Imunológico , México/epidemiologia , Proteína 2 Homóloga a MutS/genética , Estudos Retrospectivos
4.
Cell Mol Neurobiol ; 41(6): 1285-1297, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32535722

RESUMO

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case-control study was performed in 49 adult Mexican patients with grade II-IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40-5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17-10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26-4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.


Assuntos
Angiotensinogênio/genética , Astrocitoma/genética , Neoplasias Encefálicas/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Variação Genética/genética , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genética , Adulto , Astrocitoma/epidemiologia , Astrocitoma/patologia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade
5.
Scand J Gastroenterol ; 53(2): 124-129, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29275643

RESUMO

Every year, cancer affects more than one million Latin Americans. The increasing incidence of cancer could be secondary to an aging population, westernization of life style, and urbanization. LA has among the highest incidence rates of gastric cancer, compared to other countries. In this review, different studies on gastric cancer and its relation with risks factors, such as infections, diet and life styles typical of LA, besides the different molecular alterations of that specific population (mainly at a genetic polymorphism level) are analyzed. An exhaustive research was made in PubMed, MEDLINE and Embase of the most relevant studies conducted in the last 27 years (1990-2017) in LA.


Assuntos
Biomarcadores Tumorais/análise , Infecções por Vírus Epstein-Barr/complicações , Neoplasias Gástricas/epidemiologia , Fatores Etários , Dieta , Humanos , América Latina/epidemiologia , Estilo de Vida , Polimorfismo Genético , Fatores de Risco , Neoplasias Gástricas/genética
6.
Chemotherapy ; 61(6): 313-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27119162

RESUMO

BACKGROUND: Cytarabine (Ara-C) is the primary drug in different treatment schemas for acute myeloid leukemia (AML) and requires the human equilibrative nucleoside transporter (hENT1) to enter cells. The deoxycytidine kinase (dCK) enzyme limits its activation rate. Therefore, decreased expression levels of these genes may influence the response rate to this drug. METHODS: AML patients without previous treatment were enrolled. The expression of hENT1 and dCK genes was analyzed using RT-PCR. Clinical parameters were registered. All patients received Ara-C + doxorubicin as an induction regimen (7 + 3 schema). Descriptive statistics were used to analyze data. Uni- and multivariate analyses were performed to determine factors that influenced response and survival. RESULTS: Twenty-eight patients were included from January 2011 until December 2012. Median age was 36.5 years. All patients had an adequate performance status (43% with ECOG 1 and 57% with ECOG 2). Cytogenetic risk was considered unfavorable in 54% of the patients. Complete response was achieved in 53.8%. Cox regression analysis showed that a higher hENT1 expression level was the only factor that influenced response and survival. CONCLUSIONS: These results highly suggest that the pharmacogenetic analyses of Ara-C influx may be decisive in AML patients.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Citarabina/uso terapêutico , Desoxicitidina Quinase/genética , Transportador Equilibrativo 1 de Nucleosídeo/genética , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Desoxicitidina Quinase/metabolismo , Doxorrubicina/uso terapêutico , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
7.
Rev Invest Clin ; 68(3): 154-62, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27409003

RESUMO

BACKGROUND: Hyper-CVAD is the treatment for patients with acute lymphoblastic leukemia in our institution. OBJECTIVE: To evaluate the impact of single nucleotide polymorphisms at genes associated with methotrexate metabolism on survival. METHODS: The presence of the single nucleotide polymorphisms G80A at reduced folate carrier-1 gene and C677T in the methylenetetrahydrofolate reductase gene was determined by denaturing high performance liquid chromatography and validated by sequencing. Both single nucleotide polymorphisms were evaluated in 71 healthy donors and in an exploratory pilot trial with acute lymphoblastic leukemia patients to determine the influence of these single nucleotide polymorphisms on clinical outcome. Clinical characteristics, response, and outcome were registered. A Cox regression analysis was done to evaluate factors influencing response and overall survival. RESULTS: There were no differences in the frequency of single nucleotide polymorphisms between volunteers and acute lymphoblastic leukemia patients according to the Hardy-Weinberg test. Sensitivity and specificity were 72 and 91% for the G80A, and 64 and 75% for the C677T, respectively. The multivariate analysis showed that the T-immunophenotype and the presence of single nucleotide polymorphism G80A reduced folate carrier-1 were associated with a shorter relapse-free survival and overall survival. CONCLUSIONS: The presence of G80A single nucleotide polymorphism at reduced folate carrier-1 gene in acute lymphoblastic leukemia patients was associated with a poorer prognosis.


Assuntos
Proteínas de Membrana Transportadoras/genética , Metotrexato/administração & dosagem , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cromatografia Líquida de Alta Pressão , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Metotrexato/metabolismo , México , Pessoa de Meia-Idade , Análise Multivariada , Projetos Piloto , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sensibilidade e Especificidade , Taxa de Sobrevida , Vincristina/administração & dosagem , Adulto Jovem
8.
Front Oncol ; 13: 1291286, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38260834

RESUMO

Purpose: Neurofibromatosis type 1 (NF1) is a complex, multisystem disorder that is characterized, among other features, by a higher risk of developing benign and malignant tumors. Despite NF1 being one of the most common autosomal dominant genetic disorders, data from adult individuals in several world regions remain elusive, including Hispanics. Methods: The present is a retrospective cohort study conducted among adult patients with a confirmed diagnosis of NF1 who attended a single cancer-reference center, the Instituto Nacional de Cancerología in Mexico City from 2001 to 2021. Data were extracted from electronic health records and collected in an anonymous database by an NF1-expert physician in order to obtain demographic characteristics and detailed information regarding the development of tumors among this patient subgroup. All patients with malignant tumors or with benign tumors, which severely affected their quality of life, were included in this study. Results: Patient records were reviewed from 2001 to 2021. A total of N = 29 patients met the criteria, with a higher proportion of female compared with male subjects [N = 22 (75.9%) vs. N = 7 (24.1%)]. Patients had a mean age at diagnosis of tumors of 32.2 years (SD = 11.2 years). In terms of malignant neoplasms, the most frequent malignant tumor presented by patients in this cohort was malignant peripheral nerve sheath tumors (N = 7, 24.1%), this was followed by breast cancer (n = 4, 13.8% among all patients, 18.2% among female patients). Other tumors also identified in this cohort included melanoma, gastrointestinal stromal tumors, and rectal cancer. Conclusion: In Mexico, patients diagnosed with NF1 develop diverse tumors as adults. As described in other studies, the most frequent malignant tumor in this patient population is the malignant peripheral nerve sheath tumor. Further studies are required to increase the scarce information available for adult Hispanics with NF1.

9.
Pharmacogenet Genomics ; 21(12): 894-901, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21946899

RESUMO

N-acetyltransferase 2 (NAT2) catalyzes the bioactivation and/or detoxification of drugs and carcinogens. The aim of this study was to establish the correlation between the NAT2 genotype and the acetylating phenotype in a Mexican population using sulfamethazine as a probe. From a total of 122 individuals, 73 (59.8%) were slow and 49 (40.2%) were fast acetylators. Eleven individuals (9%) had the wild-type genotype (NAT2*4/NAT2*4). The most frequent genotype was NAT2*4/NAT2*5B observed in 20.66% of individuals. In conclusion, our results show that an accurate prediction of the acetylation phenotype by genotyping can be achieved in around half of the population. Further studies with a larger number of individuals are required to establish correlations between phenotype and genotype in half of that patients having a genotype combined with slow/rapid alleles.


Assuntos
Arilamina N-Acetiltransferase/genética , Carcinógenos/farmacologia , Polimorfismo Genético , Sulfametazina/farmacocinética , Acetilação , Adulto , Idoso , Alelos , Arilamina N-Acetiltransferase/metabolismo , Feminino , Estudos de Associação Genética , Humanos , Masculino , México , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/metabolismo
10.
Food Chem ; 339: 127809, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877813

RESUMO

Thiols are important natural molecules with diverse functions, ranging from acting as antioxidants that prevent chronic diseases to contributing aromas to foods and beverages. Biological thiols such as glutathione are of particular interest due to their functional roles, which include helping maintain cellular redox homeostasis and detoxifying reactive oxygen species. However, knowledge of thiol metabolism in plants is limited to studying known compounds, whereas other important thiol-containing metabolites could also exist. This work aimed to develop a new analytical approach for screening of thiols in plants, using four vegetal examples and beginning with HPLC-MS/MS in precursor ion scan mode, after extraction and thiol-specific derivatisation with 4,4'-dithiodipyridine (DTDP). Compound identity for prospective thiols was then proposed using HPLC with high resolution MS, and verified with authentic standards. This approach could lead to prospecting studies that identify thiols with potential roles in metabolic pathways, nutritional value of vegetables, or flavouring of foods.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Análise de Alimentos/métodos , Compostos de Sulfidrila/análise , Espectrometria de Massas em Tandem/métodos , Verduras/química , Dissulfetos/química , Estudo de Prova de Conceito , Piridinas/química
11.
Bol Med Hosp Infant Mex ; 78(4): 341-345, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33938902

RESUMO

BACKGROUND: Patients with familial erythrocytosis type 2 have no increased risk of von Hippel-Lindau-associated tumors, although mutations in the VHL gene cause both pathologies. CASE REPORT: We present a case of a compound heterozygote patient with von Hippel-Lindau disease and familial erythrocytosis type 2. One of the mutations found in our patient, c.416C>G (p.Ser139Cys) of the VHL gene, has not been previously reported. This case is the second one reported where von Hippel-Lindau disease and familial erythrocytosis type 2 coexist in the same individual. CONCLUSIONS: Despite the low frequency of familial erythrocytosis type 2 in patients with von Hippel-Lindau disease, the possibility of this diagnosis should be considered to avoid unnecessary invasive studies to explain the polyglobulia in these patients and guarantee an adequate follow-up and vigilance of both diseases.


Assuntos
Policitemia , Doença de von Hippel-Lindau , Criança , Humanos , Mutação , Policitemia/congênito , Policitemia/diagnóstico , Policitemia/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/genética
12.
Anal Bioanal Chem ; 394(6): 1661-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19430963

RESUMO

A rapid and sensitive method for the speciation and quantification of glucosinolates in rapeseed is described. The method combines liquid chromatography (LC) with ion trap mass spectrometry (ITMS) detection. Electrospray ionization (ESI) has been chosen as the ionization technique for the on-line coupling of LC with ITMS. Glucosinolates are extracted from different rapeseeds with MeOH and the extracts are cleaned-up by solid phase extraction with Florisil cartridges. Aqueous extracts are injected into LC system coupled to an ITMS, leading to accurately quantify eight of the most important glucosinolates in rapeseed, by MS2 mode and confirming their structure by MS3 acquisition. All the glucosinolates found in rapeseeds provide good signals corresponding to the deprotonated precursor ion [M-H]-. The method is reliable and reproducible, and detection limits range from 0.5 nmol g(-1) to 3.7 nmol g(-1) when 200 mg of dried seeds of certified reference material are analyzed. Within-day and between-day RSD percentages range between 2.4-14.1% and 3.9-16.9%, respectively. The LC-ESI-ITMS-MS method described here allows for a rapid assessment of these metabolites in rapeseed without a desulfatation step. The overall process has been successfully applied to identify and quantify glucosinolates in rapeseed samples.


Assuntos
Brassica rapa/química , Cromatografia Líquida/métodos , Glucosinolatos/análise , Espectrometria de Massas em Tandem/métodos , Glucosinolatos/química , Estrutura Molecular , Sementes/química , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray
13.
World J Surg Oncol ; 7: 97, 2009 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-20017945

RESUMO

BACKGROUND: Germ-line mutations of the TP53 gene are known to cause Li-Fraumeni syndrome, an autosomal, dominantly inherited, high-penetrance cancer-predisposition syndrome characterized by the occurrence of a variety of cancers, mainly soft tissue sarcomas, adrenocortical carcinoma, leukemia, breast cancer, and brain tumors. METHODS: Mutation analysis was based on Denaturing high performance liquid chromatography (DHPLC) screening of exons 2-11 of the TP53 gene, sequencing, and cloning of DNA obtained from peripheral blood lymphocytes. RESULTS: We report herein on Li Fraumeni syndrome in a family whose members are carriers of a novel TP53 gene mutation at exon 4. The mutation comprises an insertion/duplication of seven nucleotides affecting codon 110 and generating a new nucleotide sequence and a premature stop codon at position 150. With this mutation, the p53 protein that should be translated lacks the majority of the DNA binding domain. CONCLUSION: To our knowledge, this specific alteration has not been reported previously, but we believe it is the cause of the Li-Fraumeni syndrome in this family.


Assuntos
Mutação em Linhagem Germinativa/genética , Síndrome de Li-Fraumeni/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Primers do DNA/química , Primers do DNA/genética , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Linhagem , Adulto Jovem
14.
PLoS One ; 14(9): e0222709, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31545835

RESUMO

The deletion of exons 9 to 12 of BRCA1 (9-12 del BRCA1) is considered a founder mutation in the Mexican population. We evaluate the usefulness of the target detection of 9-12 del BRCA1 as the first molecular diagnostic strategy in patients with Hereditary Breast and Ovarian Cancer (HBOC). We performed the genetic assessment of 637 patients with suspected HBOC. The region corresponding to the breakpoints for the 9-12 del BRCA1 was amplified by polymerase chain reaction (PCR). An analysis of the clinical data of the carriers and non-carriers was done, searching for characteristics that correlated with the deletion. The 9-12 del BRCA1 was detected in 5% of patients with suspected HBOC (30/637). In patients diagnosed with ovarian cancer, 13 of 30 were 9-12 del BRCA1 carriers, which represents 43%. We found a significant association between the 9-12 del BRCA1 carriers with triple negative breast cancer and high-grade papillary serous ovarian cancer. We concluded that the detection of the 9-12 del BRCA1 is useful as a first molecular diagnostic strategy in the Mexican population. In particular, it shortens the gap in genetic assessment in patients with triple negative breast cancer and ovarian cancer.


Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/genética , Adulto , Neoplasias da Mama/diagnóstico , Éxons/genética , Saúde da Família , Feminino , Efeito Fundador , Testes Genéticos , Humanos , México , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Deleção de Sequência , Adulto Jovem
15.
J Chromatogr A ; 1177(1): 170-4, 2008 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-18048045

RESUMO

A sensitive and specific method for determining fenitrothion and its main metabolites, 3-methyl-4-nitrophenol and fenitrooxon, in poplar leaves using deuterated isotopes as the internal standard is described. The analytes and the labeled isotopes were extracted from leaves by solid-phase microextraction and subsequently analysed by gas chromatography coupled with mass spectrometry. The method had a chromatographic run time of 17.0 min and good linearity over the range 0.01-10 mg kg(-1). The detection limits ranged between 2.5 and 0.6 microg kg(-1). The isotopic dilution technique allowed improving significantly the repetitivity even using different fibers with the same coating (RSD<5.1%). The method was applied successfully to study the persistence of fenitrothion in forestal matrices in a poplar forest after cannon spray application of the insecticide.


Assuntos
Fenitrotion/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Praguicidas/análise , Folhas de Planta/química , Árvores , Indicadores e Reagentes , Padrões de Referência , Reprodutibilidade dos Testes
16.
Med Oncol ; 25(1): 56-62, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18188716

RESUMO

Polymorphisms at the thiopurine S-methyltransferase coding gene (TPMT) determine enzyme activity and consequently, the development of toxicity secondary to thiopurines. Methods A total of 108 DNA samples from volunteer donors and 39 from patients with acute lymphoblastic leukemia (ALL) were analyzed. Genomic DNA from peripheral blood leukocytes was isolated by standard methods. TPMT gene fragments were amplified by PCR for exons 5, 7, and 10. Thereafter, these were analyzed by DHPLC for the most frequent mutant TPMT alleles. Results No elution profiles on DHPLC analysis, different from those previously reported, were documented. Frequency of functional allele polymorphisms was 17.6%, being the most frequent *3A (n = 13; 4.4%), followed by *3B (n = 5; 1.7%), *3C (n = 5; 1.7%), and *2 (n = 3; 1.0%). From 39 ALL patients, 22 were treated with thiopurines, and five from 10 with a functional polymorphism developed hematological toxicity (4 mild, 1 severe in a patient referred to our Hospital after developing pancytopenia while on treatment with thiopurine). Conclusions This is the first analysis of the polymorphisms at this gene in Mexican population. Since a direct relation has been documented within functional polymorphisms and enzyme activity, and DHPLC is a highly sensitive, rapid and efficient method, feasible to realize in any phase during the treatment of ALL patients, the routine typing of TPMT polymorphisms in the patients with ALL has been set in our Institution.


Assuntos
Metiltransferases/genética , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Alelos , Cromatografia Líquida de Alta Pressão , Humanos , México , Pessoa de Meia-Idade
17.
J Pharm Biomed Anal ; 46(4): 763-70, 2008 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-18222055

RESUMO

A liquid chromatography method was developed for the determination of some frequently prescribed selective serotonin re-uptake inhibitors (SSRI) - citalopram and fluoxetine - and its main metabolites - demethylcitalopram, didemethylcitalopram and norfluoxetine - in human urine samples, using a previous stage of solid-phase microextraction. All the extraction parameters influencing adsorption (extraction time, temperature, pH, ion strength and organic modifier addition) and desorption (desorption time and desorption solvent mixture composition) of the analytes on the fiber have been studied. A satisfactory reproducibility for extraction from urine samples (R.S.D.<10%) was obtained. The linearity for urine ranged from 0.05 to 2 mg l(-1) with limits of detection close to 0.01 mg l(-1), which cover the typical urinary concentrations obtained for citalopram, fluoxetine and their metabolites.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Citalopram/análogos & derivados , Citalopram/urina , Fluoxetina/análogos & derivados , Fluoxetina/urina , Extração em Fase Sólida/métodos , Humanos , Concentração de Íons de Hidrogênio , Concentração Osmolar , Temperatura
18.
Clin Transl Oncol ; 10(11): 768-71, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19015076

RESUMO

We present 4 case studies of patients with Down's syndrome and testicular germ-cell cancer, treated with conventional methods at the National Cancer Institute of Mexico, with similar outcomes as patients without this syndrome. There are several reports of testicular cancer arising in patients with Down's syndrome worldwide, mainly from Caucasian populations. We discuss some theories about the association and the possible increase of incidence.


Assuntos
Síndrome de Down/complicações , Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Testiculares/complicações , Anormalidades Múltiplas , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Neoplasias Encefálicas/secundário , Cisplatino/administração & dosagem , Terapia Combinada , Criptorquidismo/complicações , Etoposídeo/administração & dosagem , Evolução Fatal , Humanos , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , México , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Embrionárias de Células Germinativas/cirurgia , Orquiectomia , Indução de Remissão , Neoplasias Retroperitoneais/radioterapia , Neoplasias Retroperitoneais/secundário , Seminoma/complicações , Seminoma/patologia , Seminoma/radioterapia , Seminoma/cirurgia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Resultado do Tratamento , Adulto Jovem
19.
PLoS One ; 13(11): e0206590, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30383794

RESUMO

INTRODUCTION: Renin-angiotensin system (RAS) in brain cancer represents a scarcely explored field in neuro-oncology. Recently, some pre- and clinical studies have reported that RAS components play a relevant role in the development and behavior of gliomas. The angiotensinogen (AGT) rs5050 genetic variant has been identified as a crucial regulator of the transcription of AGT mRNA, which makes it a logical and promising target of research. The aim of this study was to determine the relationship between the AGT rs5050 genetic variant in blood with prognosis in astrocytoma. METHODS: A prospective pilot study was performed on forty-eight astrocytoma patients, who received the standard-of-care treatment. Blood samples were taken prior to surgery and DNA was sequenced using Ion Torrent next-generation sequencing and analyzed by Ion Reporter software. Descriptive, bivariate, multivariate, and survival analyses were performed using SPSS v21, STATA 12 and GraphPad Prism 7. RESULTS: Median follow-up was 41 months (range 1-48). Survival analysis showed a significant difference between the rs5050 genotypes (p = .05). We found lower survival rates in individuals with the GG-genotype of rs5050 AGT compared to patients with the TT- and TG-genotype (2 months vs. 11.5 months, respectively [p = .01]). In bivariate and multivariate analyses, GG-genotype was negatively associated with survival. CONCLUSIONS: In patients with astrocytoma, AGT rs5050 GG-genotype was associated with poor prognosis. We propose this germline genetic variant as a complementary biomarker, which can be detected practically and safely in blood samples or saliva.


Assuntos
Angiotensinogênio/genética , Astrocitoma/diagnóstico , Astrocitoma/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Mutação em Linhagem Germinativa , Adulto , Idoso , Angiotensinogênio/sangue , Astrocitoma/mortalidade , Astrocitoma/terapia , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Feminino , Seguimentos , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Adulto Jovem
20.
Exp Clin Endocrinol Diabetes ; 125(4): 218-222, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28166591

RESUMO

Inherited mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, predispose individuals to the multiple endocrine neoplasia type 2 (MEN 2) cancer syndromes. The major component tumor of these syndromes is medullary thyroid carcinoma (MTC). To date, somatic mutations in RET have been identified in tumors from individuals with MEN 2 finding. RET M918T mutation is present in 95% of the MEN2B cases, and approximately 50% of sporadic MTCs harbor this mutation. We performed a mutational analysis in 17 cases of Medullary thyroid carcinoma, the somatic missense mutation at codon 918 of RET was found in 2 of the 17 MTCs, and one case presented MEN2 phenotype including MTC. The percentage of RET M918T mutation is similar in Mexican MTC patients to other series, although other mutations could be implicated in our population.


Assuntos
Carcinoma Neuroendócrino/genética , Mutação de Sentido Incorreto , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Substituição de Aminoácidos , Carcinoma Neuroendócrino/epidemiologia , Análise Mutacional de DNA , Feminino , Frequência do Gene , Humanos , Masculino , Metionina/genética , México/epidemiologia , Pessoa de Meia-Idade , Proto-Oncogene Mas , Treonina/genética , Neoplasias da Glândula Tireoide/epidemiologia , Adulto Jovem
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