Repositório Institucional - Unifesp :: Navegando por Palavras-chave "Colorectal cancer"

Navegando por Palavras-chave "Colorectal cancer"

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Análise do perfil lipidômico em pacientes com câncer colorretal em estádios avançados
(Universidade Federal de São Paulo (UNIFESP), 2017-07-31) Figueiredo, Adiel Goes de [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; http://lattes.cnpq.br/7314943504526739; http://lattes.cnpq.br/5873178563768279; Universidade Federal de São Paulo (UNIFESP)
Abstract In the last 10 years the incidence of colorectal cancer (CRC) has been increasing in developing countries. The search for molecular markers that reduce the need for invasive examinations for the diagnosis of colorectal cancer and the follow-up of treated patients advanced with the use of analytical technologies such as mass spectrometry (MS), which allowed the search for lipid metabolites as Candidates for probable biomarkers. The objective was to establish the lipid profile of patients with locally advanced, unresectable or metastatic colorectal cancer. Peripheral blood was collected from patients with colorectal cancer and patients with normal colonoscopy. After lipid extraction, the samples were processed and analyzed in the MALDI TOF / TOF equipment. From the data matrix, the statistical analyzes were performed by the principal component analysis methods and the least squares discriminant analysis. The importance of the variable in the projection was used to identify the ions that had the greatest discriminatory effect between the groups. Eight lipids were identified as potential biomarkers and a multiple logistic regression model was proposed to calculate the performance of the test where we observed values of AUC 0.87, sensitivity 88.33% and specificity 83.78% and for a validation test with 1000 permutations a p <0.001. The classes of lipids found were sphingolipids, glycerophospholipids and policetidia. The strength of the association between the peak intensities of these lipids and the presence of colorectal cancer make these metabolites candidates for possible biomarkers. We found that sphingolipid (m / z = 742.98869) could be a biomarker in monitoring patients with CRC. In the survival analysis, three lipids showed a prognostic value for colorectal cancer, sphingolipid (m / z = 857,11525) and policetidios (m / z = 876,20796) and glycerophospholipid (m / z = 1031.54773).
Acesso aberto (Open Access)
CEA as a prognostic index in colorectal cancer
(Associação Paulista de Medicina - APM, 1997-12-01) Forones, Nora Manoukian [UNIFESP]; Tanaka, Marcelo [UNIFESP]; Falcão, Jeane Brito [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
INTRODUCTION: The carcinoembryonic antigen, CEA, is the tumor marker most used in colorectal patients, principally during follow up after radical surgery. High serum CEA level before surgery is often associated with worse prognosis, in some studies. OBJECTIVE: The purpose of this study was to evaluate the preoperative carcinoembryonic antigen levels (CEA) and the frequency of recurrence. MATERIAL AND METHODS: Eighty-three patients with colorectal cancer at Dukes stages A, B or C were evaluated retrospectively. The patients' follow up was at least two years or to death. CEA was detemined in serum by enzyme immunoassay (Sorin Biomedica), normal value 0-5ng/mI. RESULTS: Disease recurrence was observed in 32 patients (38.5%), 13 Dukes B and 19 Dukes C. Seventy five per cent of the patients with CEA higher than 10ng/ml relapsed and 80% of the patients without recurrence had normal CEA. Disease recurrence in patients with preoperative elevated CEA occurred during the first year of follow up in 56% of the patients. CONCLUSION: Although the tumor stage is today the most valuable prognostic variable in colorectal cancer, the preoperative CEA value can provide some additional information in the prognosis of the patient.
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CYP2E1 RsaI and 96-bp insertion genetic polymorphisms associated with risk for colorectal cancer
(Funpec-editora, 2012-01-01) Silva, Tiago Donizetti da [UNIFESP]; Felipe, Aledson Vitor [UNIFESP]; Pimenta, Celia Aparecida Marques [UNIFESP]; Barao, Katia [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
We investigated a possible association between alcoholism, cigarette smoking, obesity and CYP2E1 RsaI and 96-bp insertion genetic polymorphisms with risk for colorectal cancer (CRC). Patients with CRC (70 women and 61 men) were matched for gender and age to 206 healthy controls. the mean age of the two groups was 62 years. Meat intake, cigarette smoking and alcohol drinking were assessed using a specific frequency questionnaire. the body mass index was also calculated. DNA was extracted from peripheral blood; RsaI polymorphism genotypes were evaluated by PCR-RFLP and 96-bp insertion genetic polymorphisms were evaluated by specific primers. the distributions of CYP2E1 RsaI c1/c1, c1/c2 and c2/c2 genotypes were 90.2, 9.2 and 0.6%, respectively, in controls and 83.9, 13.7 and 2.4% in CRC cases. Allele c2 was associated with increased risk for CRC [odds ratio (OR) = 1.88, 95% confidence interval (95%CI) = 1.02-3.45]. the CYP2E1 RsaI c2/c2 genotype was associated with an increased risk for rectal cancer (OR = 3.23, 95% CI = 1.26-9.03). the 96-bp insertion was slightly more frequent in the CRC group (9.3 vs 11.4%, P = 0.19), especially in females (6.4 vs 11.5%, P = 0.34). Smoking, alcohol drinking or high intake of red meat and CYP2E1 polymorphisms were not associated with increased risk for CRC. the 96-bp insertion was marginally more frequent (P = 0.07) in undernourished CRC subjects. We concluded that the risk for CRC is higher among individuals with allele c2. the CYP2E1 RsaI c2/c2 genotype was associated with an increased risk for rectal cancer.
Acesso aberto (Open Access)
DNA methylation profile of the DKK2 gene as a biomarker in patients with colorectal cancer
(Funpec-Editora, 2017) Silva, T. D. [UNIFESP]; Felipe, A. V. [UNIFESP]; Vidigal, V. M. [UNIFESP]; Saad, S. S. [UNIFESP]; Forones, N. M. [UNIFESP]
Purpose: Epigenetic changes can be detected in precancerous lesions, suggesting that may be involved in the early stages of carcinogenesis. The methylation of specifics genes has been correlated with the outcome of many different types of cancers. This study compared the levels of DNA methylation between normal and tumor tissues from patients with colorectal cancer (CRC). Methods: Candidate genes were screened using the MethylProfiler T PCR Array System and the Dickkopf-related protein 2 (DKK2) genes were selected for study. DNA methylation of these genes was assessed by polymerase chain reaction-high-resolution melting (PCR-HRM) analysis. Results: Out of the 112 patients studied, 68 were controls with a mean age (SD)of 59.9 years (13.4) and 45 were patients with CRC with a mean age (SD) of 64.6 years (13.6). Among the patients with CRC, 25 were women, 28 were diagnosed with colon cancer and 18 were diagnosed with rectal cancer. The number of patients with Stage I, II, III, and IV of the disease, as per the TNM classification, were 2 (4.3%), 20 (43.4%), 18 (39.1%), and 2 (4.3%), respectively. Furthermore, the DKK2 gene had a higher methylation profile in the CRC tissues when compared to normal mucosa (p < 0.001), whereas the methylation profile analysis was not statistically significant when comparing the stages of the disease (p = 0.078). Conclusion: The presence of differentially methylated sequences of the DKK2 gene between the groups showed that the methylation changes of these genes could potentially be prognostic and predictive markers in CRC.
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E-cadherin and metalloproteinase-1 and-7 polymorphisms in colorectal cancer
(Wichtig Editore, 2009-04-01) Lima, Jacqueline Miranda de [UNIFESP]; Souza, Lessileia Gomes de; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Purpose: E-cadherin (CDH1) and metalloproteinase (MMP) polymorphisms could play a crucial role in cancer invasion. Our aim was to investigate the influence of the -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 polymorphisms on the frequency and progression of colorectal cancer (CRC).Experimental design: A total of 130 patients with CRC and 130 noncancer controls were studied. The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism.Results: Patients with the 1 G allele and a family history of CRC showed a six times higher risk of developing CRC (OR: 6.45, 95%CI: 2.02-20.6, p=0.001). The A/A CDH1 genotype was associated with a higher risk of metastatic disease (OR: 3.43, 95%CI: 1.27-9.27, p=0.023). A higher marginal risk of metastatic disease was observed for MMP-1 genotypes 1G/1G and 1G/2G (OR: 2.97, 95%CI: 0.93-9.47, p=0.098).Conclusions: The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 single nucleotide polymorphisms did not modify the risk of CRC development. Patients with the 1G/1G or 1G/2G genotype and a family history of CRC presented a higher risk of CRC. The AA CDH1 and 1G/1G and 1G/2G MMP-1 genotypes might be associated with advanced metastatic disease, but are not markers of lymphatic metastasis. (Int J Biol Markers 2009; 24: 99-106)
Acesso aberto (Open Access)
Estudo das mutações germinativas nos genes de reparo e Epcam em pacientes com suspeita Síndrome de Lynch
(Universidade Federal de São Paulo (UNIFESP), 2018-01-29) Pimenta, Celia Aparecida Marques [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Oshima, Celina Tizuko Fujiyama; Lima, Fernanda Teresa; http://lattes.cnpq.br/8007052437699905; http://lattes.cnpq.br/0012255593371579; http://lattes.cnpq.br/7314943504526739; http://lattes.cnpq.br/5028766737923753; Universidade Federal de São Paulo (UNIFESP)
Background: Lynch syndrome (SL) is the most common inherited colorectal cancer (CRC) syndrome, representing 2 to 4% of all cases of CRC, because presenting few polyps is also known as HNPCC (nonpolypoid hereditary colorectal cancer). Most subjects with SL have at least one pathogenic mutation of the MMR (mismatch repair) genes MLH1, MSH2, MSH6 or PMS2. Objectives: Evaluate patients with CRC and gastric cancer (GC) with suspicion of SL by immunohistochemistry and sequencing of DNA repair genes, and EPCAM. Patients and methods: We analyzed 116 medical records of patients with CRC and GC related to SL with at least one of the Bethesda criteria, after an interview with a patient and consultation with a geneticist. An immunohistochemical test and a new generation sequencing (NGS) of repair genes was performed to investigate the expression of the repair proteins, EPCAM and BRAF. Results: Among the 116 patients, 95 were considered eligible. The mean age at diagnosis of CRC or CG in women was 50.7 years and in men 54.03. Regarding the tumor location, 40% presented tumor in the right colon, 60% had a moderately differentiated histological grade. Immunohistochemistry was performed to study the immunoexpression of the repair proteins in 95 samples of tumors tissue and 75.6% had absence of expression in at least 1 of the proteins. Among tumors with some mutations, 74% of the patients were younger than 50 years and 47% of the CRC were on left colon. NGS was performed on 95 blood samples. The MLH1 gene had 13% of pathogenic mutations, MSH2 7%, MSH6 5%, and EPCAM 1%. The number of patients affected by some mutation corresponded to 30% (29/95). Conclusion: The MLH1 gene mutation was the most frequent. The percentage of pathogenic mutations of the EPCAM gene was very rare. Approximately 50% of the patients with absence of expression of the repair genes presented pathogenic mutation at sequencing. This difference reinforces the importance of the sequencing study among patients with altered expression of repair proteins.
Acesso aberto (Open Access)
Estudo de biomarcadores lipídicos de pacientes portadores de câncer colorretal
(Universidade Federal de São Paulo (UNIFESP), 2016-07-26) Serafim, Patricia Valéria Pereira [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; http://lattes.cnpq.br/7314943504526739; http://lattes.cnpq.br/2993590347466836; Universidade Federal de São Paulo (UNIFESP)
Introduction: Colorectal cancer is one of the most prevalent cancer worldwide. In recent decades, the study of specific biomarkers aiming to a personal therapy has been the scene of several studies. The study of omics, more recently lipidomics has the purpose of analyze the individual lipids, which provides data to better understanding of human lipidome. The evolution of mass spectrometry methods such as technology for MALDI-MS, enabled the detection and identification of a wide variety of lipids with great potential to open new avenues for predictive and preventive medicine. Objective: To determine the lipidomic profile of patients with colorectal cancer in stages I, II and III, of patients with polyps and a control group. Compare the profiles of cancer patients in the preoperative to the postoperative. Patients and methods: We selected 107 patients, 40 with colorectal cancer prior to surgical resection, 23 patients after surgical resection, 12 patients with adenomatous polyp and 32 patients with normal colonoscopy. All patients were subjected to samples of peripheral blood, it was subsequently carried out extraction of the lipid from the plasma. The samples were analyzed by MALDI-MS technique for identifying lipids. Results: Using the method of analysis of variance (ANOVA) revealed differences between groups cancer and controls as well as polyps and controls. The Ion 810.1 was the one that best differentiated the groups, with p <0.01 and accuracy of 85% by PLSDA method. Among the 15 VIP lipids VIP, eight have been identified as potential biomarkers. The polyketide (810.1) was the hypo-represented lipid in cancer and over-represented in the polyp and control. The lipid profile of individuals with cancer compared to the same group after resection had an accuracy of 66% by PLSDA test. However when comparing the control patients to the cancer patients various lipid profiles had been observed with an accuracy of 100% for PLSDA test. The comparison of the polyp group to controls, by the PLSDA method, although it had not demonstrated difference between the groups, resulted in an accuracy of 74%. Conclusions: We identified possible lipid biomarkers among cancer patients compared with control groups and polyps. The polyketide lipid (810.1) was the best biomarker to differentiate cancer to the control group and polyps. We found no difference between the biomarkers in preoperative group compared to the postoperative as in the polyp group compared to the control.
Embargo
Estudo químico de Vicia faba (FABACEAE): estratégias de desreplicação molecular, isolamento de flavonóides e avaliação da atividade citotóxica
(Universidade Federal de São Paulo, 2024-01-26) Sipoloni, Victor Menezes [UNIFESP]; Veiga, Thiago André Moura [UNIFESP]; Medeiros, Lívia Soman de [UNIFESP]; http://lattes.cnpq.br/8190975614526360
O potencial de metabólitos secundários em ensaios clínicos associados a várias doenças tem sido relatado por muitos autores. Nos últimos anos, o uso de técnicas hifenadas impulsionou a descoberta de novos produtos naturais bioativos, promovendo estratégias mais eficazes para a investigação de substâncias conhecidas ou desconhecidas. Portanto, propusemos o uso de abordagens analíticas para a desreplicação molecular de substâncias biossintetizadas por Vicia faba (Fabaceae). Para isso, frações obtidas dos extratos etanólicos de diferentes partes do vegetal foram submetidas a ensaios citotóxicos contra linhagens celulares de leucemia humana (Jurkat, Kasumi-1, Raji e K562), e de carcinoma colorretal (HCT-116). Em seguida, através de análises por espectrometria de massas tandem (EM/EM), os dados foram analisados através da plataforma GNPS, para a construção de redes moleculares, a partir das quais foram agrupados os íons detectados através da similaridade dos espectros de massas, onde foi possível realizar anotações de substâncias pertencentes à classe dos flavonóides. Por fim, as frações citotóxicas foram submetidas a diferentes processos de purificação. As doze substâncias isoladas estão sendo caracterizadas por dados de RMN e EMAR, sendo que quatro delas foram identificadas como isoflavonóides, classe de substâncias nunca antes relatada para o gênero Vicia: duas isoflavonas e duas isoflavanonas (inéditas na literatura). As duas isoflavonas não apresentaram atividade citotóxica frente às diferentes linhagens testadas. Por outro lado, as isoflavanonas apresentaram atividade contra a linhagem HCT-116. Esses dados sugerem que a abordagem de desreplicação foi importante para promover a expansão da diversidade química do gênero em estudo, e que, além disso, pode nos oferecer substâncias com efeito citotóxico.
Acesso aberto (Open Access)
Expressão do RNAm e metilação do gene DKK2 em tecidos tumorais de câncer colorretal
(Universidade Federal de São Paulo (UNIFESP), 2018-10-25) Mamelli, Ronaldo Eliezer [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; http://lattes.cnpq.br/7314943504526739; http://lattes.cnpq.br/2774898093188734; Felipe, Aledson Vitor [UNIFESP]; http://lattes.cnpq.br/6480437733763768; Universidade Federal de São Paulo (UNIFESP)
BACKGROUND: Colorectal cancer (CRC) is the third most common neoplasm in the world. Methylation of tumor related genes in CpG islands can cause gene silencing and been involved in the development of cancer. The potential role of DKK2 as a biomarker for early diagnosis of CRC remains unclear. The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of CRC diagnosis and prognosis. PATIENTS AND METHODS: Expression of mRNAs encoding DKK2 in 35 CRC tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by High Resolution Melting (HRM) analysis. The general characteristics of the patients were collected. DKK2 methylation and expression were compared to clinical, pathological aspects and overall survival. RESULTS: Among the 35 patients studied, 18 were male, 10 were on ascending or transverse colon and 25 on descending or rectum. Among the 20 patients with high hipermethylation, 12 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and DKK2 RNA expression and clinical or pathological features. DKK2 promoter methylation (p=0.154) and DKK2 RNA expression (p=0.345) did not show significant correlation with prognostic factors for overall survival in CRC patients. CONCLUSION: DKK2 promoter methylation and mRNA expression appears to be biomarkers of cancer diagnosis but not predictors of prognosis.
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Genetic polymorphisms of vitamin D metabolism genes and serum level of vitamin D in colorectal cancer
(Wichtig Publishing, 2017) Vidigal, Veronica Marques [UNIFESP]; Nazareth Aguiar Junior, Pedro [UNIFESP]; Silva, Tiago Donizetti [UNIFESP]; de Oliveira, Juliana [UNIFESP]; Marques Pimenta, Celia Aparecida [UNIFESP]; Felipe, Aledson Vitor [UNIFESP]; Forones, Nora Manoukian [UNIFESP]
Background: The metabolism of vitamin D is complex, its receptor (VDR) and proteins encoded by the genes CYP27B2 and CYP24A1 can influence vitamin D serum levels. The aim of this study was to investigate the relationship of the polymorphisms of VDR (ApaI and BsmI), CYP27B1 and CYP24A1 with serum vitamin D levels in both forms, 25(OH)D-3 (circulating form) and 1,25(OH)(2)D-3 (active form), in colorectal cancer (CRC) patients. Methods: One hundred fifty-two CRC patients and 321 controls were included. DNA was extracted from peripheral blood. Polymorphisms of BsmI and ApaI were identified by PCR-RFLP. Those of CYP24A1 (rs6013897, rs158552 and rs17217119) and CYP27B1 (rs10877012) were determined by gene sequencing. Results: The median serum levels of circulating vitamin D were not different between CRC patients and controls
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Genetic polymorphisms of vitamin D receptor (VDR), CYP27B1 and CYP24A1 genes and the risk of colorectal cancer
(Wichtig Publishing, 2017) Vidigal, Veronica Marques [UNIFESP]; Silva, Tiago Donizetti [UNIFESP]; de Oliveira, Juliana [UNIFESP]; Marques Pimenta, Celia Aparecida [UNIFESP]; Felipe, Aledson Vitor [UNIFESP]; Forones, Nora Manoukian [UNIFESP]
Introduction: Vitamin D receptor (VDR) and proteins encoded by the genes CYP27B2 and CYP24A1 involved in the production and inactivation of vitamin D can influence vitamin D and the susceptibility to colorectal cancer (CRC). The objective of this study was to investigate the relationship between the risk of CRC and polymorphisms in VDR, CYP27B1 and CYP24A1, lifestyle and dietary habits. Methods: The study included 152 patients with CRC and 321 controls. All participants answered a questionnaire on their dietary habits, alcohol consumption and smoking habits. DNA was extracted from peripheral blood. Polymorphisms of BsmI and ApaI were identified by performing PCR-RFLP. Identification of CYP24A1 (rs6013897, rs158552 and rs17217119) and CYP27B1 (rs10877012) polymorphisms was performed by gene sequencing. Results: Smoking, alcohol use, and low or no consumption of fruit, cereals and dairy products were associated with an increased risk of CRC. A heterozygous genotype Aa or an association genotype aa + Aa of the VDR ApaI polymorphism increased the risk of CRC. The VDR BsmI polymorphism was not significantly associated with the risk of CRC. Multivariate analysis showed that heterozygous and association genotype AT + AA of the rs6013897 polymorphism, genotype CT of the rs158552 polymorphism, association genotype CT + CC and genotypes AA and GG of the rs17217119 polymorphism of CYP24A1, and heterozygous genotype GT and association genotype GT + TT of the rs10877012 polymorphism in CYP27B1 were associated with a higher risk of CRC. Conclusions: Dietary habits, lifestyle, and polymorphisms in VDR (ApaI), CYP24A1 (rs6013897, rs158552, rs17217119) and CYP27B1 (rs10877012) were associated with a higher risk of CRC.
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N-Acetyltransferase 2 genetic polymorphisms and risk of colorectal cancer
(Baishideng Publ Grp Co Ltd, 2011-02-14) Silva, Tiago Donizetti da [UNIFESP]; Felipe, Aledson Vitor [UNIFESP]; Lima, Jacqueline Miranda de [UNIFESP]; Oshima, Celina Tizuko Fujiyama [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
AIM: To investigate the possible association between meat intake, cigarette smoking and N-acetyltransferase 2 (NAT2) genetic polymorphisms on colorectal cancer (CRC) risk.METHODS: Patients with CRC were matched for gender and age to healthy controls. Meat intake and cigarette smoking were assessed using a specific frequency questionnaire. DNA was extracted from peripheral blood and the genotypes of the polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism. Five NAT2 alleles were studied (WT, M1, M2, M3 and M4) using specific digestion enzymes.RESULTS: A total of 147 patients with colorectal cancer (76 women and 90 men with colon cancer) and 212 controls were studied. the mean age of the two groups was 62 years. More than half the subjects (59.8% in the case group and 51.9% in the control group) were NAT2 slow acetylators. the odds ratio for colorectal cancer was 1.38 (95% CI: 0.90-2.12) in slow acetylators. Although the number of women was small (n = 76 in the case group), the cancer risk was found to be lower in intermediate (W/Mx) acetylators [odds ratio (OR): 0.55, 95% confidence interval (95% CI): 0.29-1.02]. This difference was not observed in men (OR: 0.56, 95% CI: 0.16-2.00). Among NAT2 fast acetylators (W/W or W/Mx), meat consumption more than 3 times a week increased the risk of colorectal cancer (OR: 2.05, 95% CI: 1.01-4.16). in contrast, cigarette smoking increased the risk of CRC among slow acetylators (OR: 1.97, 95% CI: 1.02-3.79).CONCLUSION: the risk of CRC was higher among fast acetylators who reported a higher meat intake. Slow NAT2 acetylation was associated with an increased risk of CRC. (C) 2011 Baishideng. All rights reserved.
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Preventive DNA vaccination against CEA-expressing tumors with anti-idiotypic scFv6.C4 DNA in CEA-expressing transgenic mice
(Springer, 2017) Denapoli, Priscila M. A. [UNIFESP]; Zanetti, Bianca F. [UNIFESP]; dos Santos, Adara A. [UNIFESP]; de Moraes, Jane Z. [UNIFESP]; Han, Sang W. [UNIFESP]
Carcinoembryonic antigen (CEA) is expressed during embryonic life and in low level during adult life. Consequently, the CEA is recognized by the immune system as a self-antigen and thus CEA-expressing tumors are tolerated. Previously, we constructed a single chain variable fragment using the 6.C4 (scFv6.C4) hybridoma cell line, which gave rise to antibodies able to recognize CEA when C57/Bl6 mice were immunized. Here, the scFv6.C4 ability to prevent the CEA-expressing tumor growth was assessed in CEA-expressing transgenic mice CEA2682. CEA2682 mice immunized with the scFv6.C4 expressing plasmid vector (uP/PS-scFv6.C4) by electroporation gave rise to the CEA-specific AB3 antibody after the third immunization. Sera from immunized mice reacted with CEA-expressing human colorectal cell lines CO112, HCT-8, and LISP-1, as well as with murine melanoma B16F10 cells expressing CEA (B16F10-CEA). Cytotoxic T lymphocytes (CTL) from uP/PS-scFv6.C4 immunized mice lysed B16F10-CEA (56.7%) and B16F10 expressing scFv6.C4 (B16F10-scFv6.C4) (46.7%) cells, against CTL from uP-immunized mice (10%). After the last immunization, 5 x 10(5) B16F10-CEA cells were injected into the left flank. All mice immunized with the uP empty vector died within 40 days, but uP/PS-scFv6.C4 vaccinated mice (40%) remained free of tumor for more than 100 days. Splenocytes obtained from uP/PS-scFv6.C4 vaccinated mice showed higher T-cell proliferative activity than those from uP vaccinated mice. Collectively, DNA vaccination with the uP-PS/scFv6.C4 plasmid vector was able to give rise to specific humoral and cellular responses, which were sufficient to retard growth and/or eliminate the injected B16F10-CEA cells.
Acesso aberto (Open Access)
Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients
(Baishideng Publishing Group Inc, 2017) do Espirito Santo, Gilmar Ferreira [UNIFESP]; Galera, Bianca Borsatto; Duarte, Elisabeth Carmen; Chen, Elisabeth Suchi [UNIFESP]; Azis, Lenuce; Damazo, Amilcar Sabino; Saba, Gabriela Tognini [UNIFESP]; Gehrke, Flavia de Sousa; Cotrim Guerreiro da Silva, Ismael Dale [UNIFESP]; Waisberg, Jaques [UNIFESP]
AIM To investigate the associations of the genetic polymorphisms of vascular endothelial growth factor A (VEGF-A) -1498C> T and -634G> C, with the survival of patients with colorectal cancer (CRC). METHODS A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction (PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A -1498C> T (rs833031) and -634G> C (rs2010963) polymorphisms. Genotyping was validated for VEGF-A -1498C> T polymorphism in 129 patients and for VEGF-A -634G> C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method. RESULTS In the univariate analysis there was a significant association (OR = 0.32
Acesso aberto (Open Access)
What are the most effective methods for assessment of nutritional status in outpatients with gastric and colorectal cancer?
(Aula Medica Ediciones, 2013-05-01) Vicente, Mariana Abe [UNIFESP]; Barao, Katia [UNIFESP]; Silva, Tiago Donizetti [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Objective: To evaluate methods for the identification of nutrition risk and nutritional status in outpatients with colorectal (CRC) and gastric cancer (GC), and to compare the results to those obtained for patients already treated for these cancers.Methods: A cross-sectional study was conducted on 137 patients: group 1 (n = 75) consisting of patients with GC or CRC, and group 2 (n = 62) consisting of patients after treatment of GC or CRC under follow up, who were tumor free for a period longer than 3 months. Nutritional status was assessed in these patients using objective methods [body mass index (BMI), phase angle, serum albumin]; nutritional screening tools [Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST), Nutritional Risk Index (NRI)], and subjective assessment [Patient-Generated Subjective Global Assessment (PG-SGA)]. the sensitivity and specificity of each method was calculated in relation to the PG-SGA used as gold standard.Results: One hundred thirty seven patients participated in the study. Stage IV cancer patients were more common in group 1. There was no difference in BMI between groups (p = 0.67). Analysis of the association between methods of assessing nutritional status and PG-SGA showed that the nutritional screening tools provided more significant results (p < 0.05) than the objective methods in the two groups. PG-SGA detected the highest proportion of undernourished patients in group 1. the nutritional screening tools MUST, NRI and MST were more sensitive than the objective methods. Phase angle measurement was the most sensitive objective method in group 1.Conclusion: the nutritional screening tools showed the best association with PG-SGA and were also more sensitive than the objective methods. the results suggest the combination of MUST and PG-SGA for patients with cancer before and after treatment.

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