Analysis of the TSER and G>C variants in the TYMS gene: a high frequency of low expression genotypes predicted in the Mexican population.

BACKGROUND: In the TYMS gene promoter, there is a repeat polymorphism (TSER) that affects the expression level of the thymidylate synthetase (TS) enzyme involved in the response to some anticancer drugs. The G>C transversion located in the TSER*3R allele decreases the expression level of the TS enzyme avoiding the upstream stimulatory factor (USF-1) binding site. Despite the biomedical impact of the SNP G>C, only TSER has been reported in most worldwide populations. Thus, we studied both TSER and SNP G>C variants in the Mexican population. SUBJECTS AND METHODS: A population sample (n = 156) was genotyped for the TSER and G>C variants by PCR and PCR-RFLPs, respectively, followed by PAGE and silver staining. RESULTS: For TSER, the most frequent allele was 2 R (52.56%), as well as the genotype 2 R/3R (42.3%). Comparison with Latin American, European, and American (USA) populations suggest a heterogeneous worldwide distribution (FST-value = 0.01564; p-value = 0.0000). When the G>C variant was included (2RG, 3RG, and 3RC), a high frequency of low expression genotypes was observed: 2RG/2RG, 2RG/3RC, and 3RC/3RC (84.6%). CONCLUSION: The high frequency of genotypes associated with low TS enzyme expression justifies obtaining the TYMS gene variant profile in Mexican patient's candidates to pharmaceutical treatments like 5'-Fluoracil, methotrexate, and pemetrex.

Secretion of biologically active pancreatitis-associated protein I (PAP) by genetically modified dairy Lactococcus lactis NZ9000 in the prevention of intestinal mucositis.

BACKGROUND: Mucositis is one of the most relevant gastrointestinal inflammatory conditions in humans, generated by the use of chemotherapy drugs, such as 5-fluoracil (5-FU). 5-FU-induced mucositis affects 80% of patients undergoing oncological treatment causing mucosal gut dysfunctions and great discomfort. As current therapy drugs presents limitations in alleviating mucositis symptoms, alternative strategies are being pursued. Recent studies have shown that the antimicrobial pancreatitis-associated protein (PAP) has a protective role in intestinal inflammatory processes. Indeed, it was demonstrated that a recombinant strain of Lactococcus lactis expressing human PAP (LL-PAP) could prevent and improve murine DNBS-induced colitis, an inflammatory bowel disease (IBD) that causes severe inflammation of the colon. Hence, in this study we sought to evaluate the protective effects of LL-PAP on 5-FU-induced experimental mucositis in BALB/c mice as a novel approach to treat the disease. RESULTS: Our results show that non-recombinant L. lactis NZ9000 have antagonistic activity, in vitro, against the enteroinvasive gastrointestinal pathogen L. monocytogenes and confirmed PAP inhibitory effect against Opportunistic E. faecalis. Moreover, L. lactis was able to prevent histological damage, reduce neutrophil and eosinophil infiltration and secretory Immunoglobulin-A in mice injected with 5-FU. Recombinant lactococci carrying antimicrobial PAP did not improve those markers of inflammation, although its expression was associated with villous architecture preservation and increased secretory granules density inside Paneth cells in response to 5-FU inflammation. CONCLUSIONS: We have demonstrated for the first time that L. lactis NZ9000 by itself, is able to prevent 5-FU-induced intestinal inflammation in BALB/c mice. Moreover, PAP delivered by recombinant L. lactis strain showed additional protective effects in mice epithelium, revealing to be a promising strategy to treat intestinal mucositis.

Investigation of Binding Behavior between Drug Molecule 5-Fluoracil and M4 L4 -Type Tetrahedral Cages: Selectivity, Capture, and Release.

Two analogous M4 L4 -type tetrahedral cages (smaller: MOC-19; larger: MOC-22) were synthesized and investigated for their interactions with the anticancer drug 5-fluoracil (5-FU) by NMR spectroscopy, high-resolution electrospray-ionization mass spectrometry (HR-ESI-MS), and molecular simulation. The cage's size and window are of importance for the host-guest binding, and consequently the smaller MOC-19 with a more suitable size of cavity window was found to have much stronger hydrogen-bond interactions with 5-FU. The porous nanoparticles of MOC-19 exhibited outstanding behavior for the controlled release of 5-FU in a simulated human body with liquid phosphate-buffered saline solution.

Depressive symptoms and cognitive deficits in a cancer patient submitted to chemotherapy with 5-Fluoracil: a case report / Sintomas depressivos e déficits cognitivos em paciente com câncer submetido a quimioterapia com 5-fluoracil: relato de caso

Cognitive deficits in cancer patients can be related to depression, anxiety, and the side effects of treatments such as fatigue. In this case report, we described an elderly patient with rectal adenocarcinoma, which presented depressive symptoms and memory complaints after treatment with 5-Fluoracil and Leucovorin. Depressive symptoms improved after two months but cognitive and functional impairment worsened suggesting the diagnosis of mild dementia. Structural and functional brain changes were seen on neuroimaging exams. Rivastigmine was introduced up to 12 mg/day, and after a one-year follow up the patient remained stable. Cognitive deficits can be a consequence of cancer therapies and a protocol to investigate deficits cognitive could be useful to the diferential diagnosis and management of elderly cancer patients submitted to chemotherapy.

Déficits cognitivos em pacientes com câncer podem estar relacionados à depressão, ansiedade e aos efeitos colaterais dos tratamentos, como fadiga. Neste relato de caso, descrevemos um paciente idoso com adenocarcinoma do reto, que apresentou sintomas depressivos e queixas de memória, após o tratamento com 5-Fluoracil e Leucovorin. Os sintomas depressivos melhoraram após dois meses, mas o comprometimento cognitivo e functional pioraram, sugerindo o diagnóstico de demência leve. Mudanças cerebrais estruturais e funcionais foram vistos em exames de neuroimagem. Rivastigmina foi introduzida até 12 mg/dia, e após um ano de seguimento o paciente permanecia estável. Déficits cognitivos podem ser consequência das terapias anti-neoplásicas e um protocolo para investigar déficits cognitivos pode ser útil para o diagnóstico diferencial e manejo de pacientes idosos com câncer submetidos à quimioterapia.

Depressive symptoms and cognitive deficits in a cancer patient submitted to chemotherapy with 5-Fluoracil: a case report.

Cognitive deficits in cancer patients can be related to depression, anxiety, and the side effects of treatments such as fatigue. In this case report, we described an elderly patient with rectal adenocarcinoma, which presented depressive symptoms and memory complaints after treatment with 5-Fluoracil and Leucovorin. Depressive symptoms improved after two months but cognitive and functional impairment worsened suggesting the diagnosis of mild dementia. Structural and functional brain changes were seen on neuroimaging exams. Rivastigmine was introduced up to 12 mg/day, and after a one-year follow up the patient remained stable. Cognitive deficits can be a consequence of cancer therapies and a protocol to investigate deficits cognitive could be useful to the diferential diagnosis and management of elderly cancer patients submitted to chemotherapy.

Déficits cognitivos em pacientes com câncer podem estar relacionados à depressão, ansiedade e aos efeitos colaterais dos tratamentos, como fadiga. Neste relato de caso, descrevemos um paciente idoso com adenocarcinoma do reto, que apresentou sintomas depressivos e queixas de memória, após o tratamento com 5-Fluoracil e Leucovorin. Os sintomas depressivos melhoraram após dois meses, mas o comprometimento cognitivo e functional pioraram, sugerindo o diagnóstico de demência leve. Mudanças cerebrais estruturais e funcionais foram vistos em exames de neuroimagem. Rivastigmina foi introduzida até 12 mg/dia, e após um ano de seguimento o paciente permanecia estável. Déficits cognitivos podem ser consequência das terapias anti-neoplásicas e um protocolo para investigar déficits cognitivos pode ser útil para o diagnóstico diferencial e manejo de pacientes idosos com câncer submetidos à quimioterapia.

Clinical and epidemiological evaluation of patients with colorectal cancer from Rio Grande do Sul

Colorectal cancer has a high incidence in Brazil, with the South and Southeast regions presenting the largest number of cases. OBJECTIVE: Identify the epidemiological characteristics and the regimens used as first-line treatment of patients with colorectal cancer treated at a cancer center in Santa Cruz do Sul (RS, Brazil) from 2006 to 2011. METHODS: The records of 130 patients were retrospectively evaluated. Clinical and epidemiological characteristics, such as age, gender, ethnic group, stage of disease, primary site of disease and first-line treatment, were evaluated. The association of significance was evaluated using the chi-square and Fischer exact tests. The confidence interval used was 95% (p<0.05). RESULTS: The mean age of patients with colorectal cancer in this study was 60.8 years, with higher incidence of the disease in men. At diagnosis, 40% of the patients had advanced disease stage IV. The regimen of 5-fluorouracil/folic acid (68.5%) was used as first-line treatment. CONCLUSION: This study showed high prevalence of colorectal cancer in patients of advanced age with the diagnosis made in the later stage of the disease. This fact demonstrates the importance of prevention campaigns that encourage periodic examinations in patients over 50 years of age. (AU)

No Brasil, o câncer colorretal apresenta uma elevada incidência, sendo as Regiões Sul e Sudeste as com maior número de casos. OBJETIVO: Identificar as características epidemiológicas e os esquemas terapêuticos utilizados como primo-tratamento dos pacientes portadores de câncer colorretal atendidos em um centro especializado em oncologia em Santa Cruz do Sul (RS) no período de 2006 a 2011. MÉTODO: Foram avaliados retrospectivamente 130 prontuários de pacientes portadores de câncer colorretal. Características clínicas e epidemiológicas como idade, sexo, cor da pele, estádio da doença, sítio primário da doença e primo-tratamento foram avaliadas. A associação de significância foi avaliada pelos testes do qui-quadrado e exato de Fischer. O intervalo de confiança utilizado foi de 95% (p<0,05). RESULTADOS: A idade média dos pacientes encontrada neste estudo foi de 60,8 anos com incidência maior da doença entre os homens. No momento do diagnóstico, 40% dos pacientes estavam com a doença no estádio IV. Como primo-tratamento o esquema terapêutico mais utilizado foi o 5-fluoracil/ácido folínico (68,5%). CONCLUSÃO: Este estudo ratificou a alta prevalência do câncer colorretal em pacientes com idade mais avançada, com o diagnóstico realizado na fase mais avançada da doença. Esse fato evidencia a importância da realização de campanhas de prevenção que estimulem a realização de exames periódicos nos pacientes com idade acima de 50 anos. (AU)