RNAM EXPRESSION AND DNA METHYLATION OF DKK2 GENE IN COLORECTAL CÂNCER.

BACKGROUND: Colorectal cancer 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 colorectal cancer remains unclear. OBJECTIVE: The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of colorectal cancer diagnosis and prognosis. METHODS: Expression of mRNAs encoding DKK2 in 35 colorectal cancer tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by high resolution melting 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 right colon and 25 on left colon. Among the 20 patients with high hypermethylation, 15 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and mRNA DKK2 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 overall survival. CONCLUSION: DKK2 promoter methylation and DKK2 RNA status appear to be biomarkers of cancer diagnosis but not predictors of prognosis.

Expressão do RNAm e metilação do DNA do gene DKK2 em câncer colorretal / Rnam expression and dna methylation of dkk2 gene in colorectal câncer

ABSTRACT BACKGROUND: Colorectal cancer 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 colorectal cancer remains unclear. OBJECTIVE: The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of colorectal cancer diagnosis and prognosis. METHODS: Expression of mRNAs encoding DKK2 in 35 colorectal cancer tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by high resolution melting 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 right colon and 25 on left colon. Among the 20 patients with high hypermethylation, 15 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and mRNA DKK2 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 overall survival. CONCLUSION: DKK2 promoter methylation and DKK2 RNA status appear to be biomarkers of cancer diagnosis but not predictors of prognosis.

RESUMO CONTEXTO: O câncer colorretal é a terceira neoplasia mais comum no mundo. A metilação de alguns genes nas ilhas CpG podem causar silenciamento gênico e estar envolvida no desenvolvimento de câncer. O potencial papel de DKK2 como um biomarcador no diagnóstico precoce de CCR permanece incerto. OBJETIVO: O objetivo do estudo foi avaliar o perfil de metilação e expressão de RNAm do gene DKK2 para identificar preditores potenciais de diagnóstico e prognóstico de CCR. MÉTODOS: A expressão de mRNAs que codificam DKK2 em 35 tecidos de câncer colorretal foi quantificada por reação em cadeia da polimerase em tempo real e a metilação do DNA foi verificada por análise de alta resolução. As características gerais dos pacientes foram coletadas. A metilação e expressão de DKK2 foram comparadas aos aspectos clínicos, patológicos e à sobrevida global. RESULTADOS: Entre os 35 pacientes estudados, 18 eram do sexo masculino, 10 tumores eram do cólon ascendente ou transverso e 25 do descendente ou reto. Entre os 20 pacientes com hipermetilação, 12 deles apresentaram baixa expressão de RNAm do gene DKK2. Não houve associação significativa entre a metilação do promotor de DKK2 e a expressão de RNAm de DKK2 e características clínicas ou patológicas. A metilação do promotor de DKK2 e a expressão do RNA de DKK2 não mostraram correlação com sobrevida global dos pacientes com CCR. CONCLUSÃO: A metilação do gene promotor e a expressão do RNAm do gene DKK2 parecem ser biomarcadores de diagnóstico de câncer, mas não se mostraram úteis na avaliação prognóstica.

High-resolution melting for detecting KRAS mutations in colorectal cancer.

Colorectal cancer is a leading cause of cancer that may metastasize. KRAS gene sequence of exon 2 should be examined for identification of patients that can be treated with anti-EGFR. The aim of the present study was to evaluate the efficacy of high-resolution melting (HRM) to detect KRAS mutations in colorectal cancer (CRC) tumors. The exon 2 of KRAS was amplified from 47 adenocarcinoma CRC tissues. The tumors were subjected to high-resolution melt using quantitative PCR to identify wild-type and mutant subgroups. The results were compared to the mutations detected by next-generation sequences (NGS). The study included 47 patients, with a mean age of 62 years, of whom 24 patients were male. Most of the patients had stage II or stage III tumors. The mean melting temperatures for the wild-type and mutated group at exon 2 were 78.13˚C and 77.87˚C, respectively (P<0.001, 95% CI = 0.11-0.4). The sensitivity and specificity of high-resolution melting were 83.3 and 96.6%, respectively, with a high concordance between the NGS and HRM methods for detecting KRAS mutation in exon 2 (ĸ = 0.816; P=0.625). Thus, HRM could be used as an alternative method for detecting KRAS mutations in colorectal cancer tissue.

Fecal Genetic Mutations and Human DNA in Colorectal Cancer and Polyps Patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent cancers. Genetic mutations in CRC already described can be detected in feces. Microarray methods in feces can represent a new diagnostic tool for CRC and significant improvement at public health. AIM: to analyze stool DNA by human DNA quantify and microarray methods as alternatives to CRC screening. METHOD: Three methods were analyzed in stool samples: Human DNA Quantify, RanplexCRC and KRAS/BRAF/PIK3CA (KBP) Arrays. RESULTS: KBP array mutations were presented in 60.7% of CRC patients and RanplexCRC Array mutations in 61.1% of CRC patients. Sensitivity and specificity for human DNA quantification was 66% and 82% respectively. Fecal KBP Array had 35% sensitivity and 96% specificity and RanplexCRC Array method had 78% sensitivity and 100% specificity. CONCLUSION: Microarray methods showed promise as potential biomarkers for CRC screening; however, these methods had to be optimized to improve accuracy and applicability by clinical routine.

ADIPONECTIN, VITAMIN D AND NUTRITIONAL STATUS IN PATIENTS WITH ADVANCED COLORECTAL CANCER OR DURING FOLLOW-UP.

BACKGROUND: Considering the high incidence of colorectal cancer (CRC) related deaths, many studies have investigated variables that can affect survival, with the aim of prolonging survival. The nutritional status can also be predict survival in patients with CRC. OBJECTIVE: The aim of the present study was to evaluate if BMI, %FAT, PhA, PG-SGA, adiponectin levels, and vitamin D levels are relevant to the characterization and differentiation of patients with advanced CRC and patients with a history of CRC. METHODS: The study was carried out by patients with advanced colorectal cancer (Group 1) and patients in follow-up after colorectal cancer treatment (Group 2). Nutritional status was assessed using the body mass index, body fat percentage, phase angle from bioelectrical impedance, Patient-Generated Subjective Global Assessment score. Adiponectin concentrations were determined using an enzyme-linked immunosorbent assay, and vitamin D levels were measured using high performance liquid chromatography. RESULTS: Groups 1 and 2 consisted of 23 and 27 patients, respectively. The body mass index, body fat percentage, phase angle, vitamin D and adiponectin levels were not significantly different between the groups. The mean Patient-Generated Subjective Global Assessment score was significantly higher in group 1 compared with group 2, and was significantly correlated with the long-term mortality risk. CONCLUSION: Among the nutritional status parameters, only the Patient-Generated Subjective Global Assessment score was significantly different between the groups and was an important predictor of survival in patients with advanced colorectal cancer.

Impact of genetic mutations and nutritional status on the survival of patients with colorectal cancer.

BACKGROUND: The prognosis of colorectal cancer (CRC) patients can be influenced by genetic mutations and nutritional status. The relationship between these variables is unclear. The objective of the study was to verify the variables involved in the nutritional status and genetic mutations, which correlate with survival of CRC patients. METHODS: Patients with surgical intervention for tumor resection were evaluated using body mass index, nutritional screening, patient self-produced global subjective assessment, phase angle, and computed tomography to calculate the areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue, and muscle mass for the determination of sarcopenia. Ten gene mutations involved in CRC carcinogenesis were studied (PIK3CA, KRAS, BRAF, EGFR, NRAS, TP53, APC, PTEN, SMAD4, and FBXW7). DNA was extracted from fresh tumor or paraffin tissues. RESULTS: Of the 46 patients, 29 (64.4%) were at nutritional risk and 21 (45.7%) were moderately malnourished. However, there was a high percentage of VAT in 24 (61.5%) and sarcopenia in 19 (48.7%) patients. These variables were associated with a higher risk of mortality. Nutritional risk, moderate or severe malnutrition, phase angle < 5°, VAT < 163.8 cm2 in men and <  80.1 cm2 in women, and sarcopenia were associated with the relative risk of death, with respective hazard ratios/odds ratios and 95% confidence intervals of 8.77 (1.14-67.1), 3.95 (1.11-14.0), 3.79 (1.10-13.1), 3.43 (1.03-11.4), and 3.95 (1.06-14.6). Increased VAT was associated with a lower risk of death, even in patients older than 60 years or those harboring mutated KRAS. CONCLUSIONS: Patients with positive indicators for malnutrition or risk of malnutrition had an increased risk of death. No relationship was identified between the presence of mutations and survival.

Adiponectina, vitamina D e estado nutricional em pacientes com câncer colorretal avançado e em seguimento / Adiponectin, vitamin d and nutritional status in patients with advanced colorectal cancer or during follow-up

ABSTRACT BACKGROUND: Considering the high incidence of colorectal cancer (CRC) related deaths, many studies have investigated variables that can affect survival, with the aim of prolonging survival. The nutritional status can also be predict survival in patients with CRC. OBJECTIVE: The aim of the present study was to evaluate if BMI, %FAT, PhA, PG-SGA, adiponectin levels, and vitamin D levels are relevant to the characterization and differentiation of patients with advanced CRC and patients with a history of CRC. METHODS: The study was carried out by patients with advanced colorectal cancer (Group 1) and patients in follow-up after colorectal cancer treatment (Group 2). Nutritional status was assessed using the body mass index, body fat percentage, phase angle from bioelectrical impedance, Patient-Generated Subjective Global Assessment score. Adiponectin concentrations were determined using an enzyme-linked immunosorbent assay, and vitamin D levels were measured using high performance liquid chromatography. RESULTS: Groups 1 and 2 consisted of 23 and 27 patients, respectively. The body mass index, body fat percentage, phase angle, vitamin D and adiponectin levels were not significantly different between the groups. The mean Patient-Generated Subjective Global Assessment score was significantly higher in group 1 compared with group 2, and was significantly correlated with the long-term mortality risk. CONCLUSION: Among the nutritional status parameters, only the Patient-Generated Subjective Global Assessment score was significantly different between the groups and was an important predictor of survival in patients with advanced colorectal cancer.

RESUMO CONTEXTO: Considerando a alta incidência de óbitos devido ao câncer coloretal (CCR), estudos investigaram variáveis que podem afetar a sobrevida, com objetivo de prolongar a sobrevida. O estado nutricional desses pacientes também pode predizer a sobrevida. OBJETIVO: O objetivo do presente estudo foi avaliar se o índice de massa corporal (IMC), a porcentagem de gordura, os níveis séricos de adiponectina e de vitamina D são relevantes para a caracterização e diferenciação de pacientes com CCR avançado e pacientes com histórico de CCR. MÉTODOS: O estudo foi realizado por pacientes com câncer colorretal avançado (Grupo 1) e pacientes em acompanhamento após o tratamento do CCR (Grupo 2). O estado nutricional foi avaliado por meio do IMC, percentual de gordura corporal, ângulo de fase da bioimpedância elétrica, escore de Avaliação Global Subjetiva Gerada pelo Paciente. As concentrações de adiponectina foram determinadas por ELISA e os níveis de vitamina D foram medidos por meio de cromatografia líquida de alta performance. RESULTADOS: Os grupos 1 e 2 consistiram de 23 e 27 pacientes, respectivamente. O IMC, percentual de gordura corporal, ângulo de fase, níveis de vitamina D e adiponectina não foram significativamente diferentes entre os grupos. O escore médio da Avaliação Global Subjetiva Gerada pelo Paciente foi significativamente maior no grupo 1 em comparação com o Grupo 2, e foi significativamente correlacionado com o risco de mortalidade a longo prazo. CONCLUSÃO: Entre os indicadores do estado nutricional, apenas o escore da Avaliação Global Subjetiva Gerada pelo Paciente foi significativamente diferente entre os grupos e foi um importante preditor de sobrevida em pacientes com câncer colorretal avançado.

Heparan Sulfate Proteoglycans in Human Colorectal Cancer.

Colorectal cancer is the third most common cancer worldwide, accounting for more than 610,000 mortalities every year. Prognosis of patients is highly dependent on the disease stage at diagnosis. Therefore, it is crucial to investigate molecules involved in colorectal cancer tumorigenesis, with possible use as tumor markers. Heparan sulfate proteoglycans are complex molecules present in the cell membrane and extracellular matrix, which play vital roles in cell adhesion, migration, proliferation, and signaling pathways. In colorectal cancer, the cell surface proteoglycan syndecan-2 is upregulated and increases cell migration. Moreover, expression of syndecan-1 and syndecan-4, generally antitumor molecules, is reduced. Levels of glypicans and perlecan are also altered in colorectal cancer; however, their role in tumor progression is not fully understood. In addition, studies have reported increased heparan sulfate remodeling enzymes, as the endosulfatases. Therefore, heparan sulfate proteoglycans are candidate molecules to clarify colorectal cancer tumorigenesis, as well as important targets to therapy and diagnosis.

Reversal of Multidrug Resistance in an Epirubicin-Resistant Gastric Cancer Cell Subline

Background: Gastric cancer is one of the most common malignancies worldwide. Epirubicin (EPI) is used extensively in the treatment of multiple cancers despite its tendency to induce multidrug resistance though overexpression of the ABCB1 efflux pump. However, this overexpression can be disrupted using short interfering RNAs (siRNAs). Objective and Methods: The aim of this study was to explore approaches to reverse EPI resistance and thus increase the success of chemotherapy treatment in an EPI-resistant gastric cancer cell subline (AGS/EPI). Methods: The study focused on effects of ABCB1 knockdown by siRNA technology using TaqMan gene expression assays with quantitative real-time reverse-transcription PCR (qRT-PCR). MTT assays were performed to evaluate viability and prolifer in subline. ABCB1 protein localization and EPI intracellular fluorescence intensity in AGS/EPI cells were detected by confocal microscopy. Results: The siRNA efficiently downregulated ABCB1 mRNA in AGS/EPI cells. Thus MDR reversal was clearly demonstrated in the AGS/EPI cells, offering the possibility of future in vitro chemoresistance assays for the GC field. Conclusions: ABCB1 knockdown decreased EPI efflux and increased EPI sensitivity in AGS/EPI cells. This result provides a novel strategy for targeted gene therapy to reverse EPI resistance in gastric cancer.

Genetic polymorphisms of vitamin D receptor (VDR), CYP27B1 and CYP24A1 genes and the risk of colorectal cancer.

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.

HUMAN DNA QUANTIFICATION IN THE STOOLS OF PATIENTS WITH COLORECTAL CANCER

Background - Colorectal cancer is one of the main cause of cancer in the world. Colonoscopy is the best screen method, however the compliance is less than 50%. Quantification of human DNA (hDNA) in the feces may be a possible screen non-invasive method that is a consequence of the high proliferation and exfoliation of cancer cells. Objective - To quantify the human DNA in the stools of patients with colorectal cancer or polyps. Methods - Fifty patients with CRC, 26 polyps and 53 with normal colonoscopy were included. Total and human DNA were analyzed from the frozen stools. Results - An increased concentration of hDNA in the stools was observed in colorectal cancer patients compared to controls and polyps. Tumors localized in the left side of the colon had higher concentrations of hDNA. There were no difference between polyps and controls. A cut off of 0.87 ng/mL of human DNA was determined for colorectal cancer patients by the ROC curve, with a sensitivity of 66% and a specificity of 86.8%. For polyps the cut off was 0.41, the sensitivity was 41% and the specificity 77.4%. Conclusion - A higher concentration of hDNA had been found in colorectal cancer patients The quantification of hDNA from the stools can be a trial method for the diagnosis of colorectal cancer.

Contexto - O câncer colorretal é, mundialmente, uma das principais causas de câncer. A colonoscopia é o melhor método de rastreamento, no entanto a adesão é inferior a 50%. A quantificação de DNA humano (hDNA) nas fezes pode ser um possível método não invasivo de rastreamento, que é consequência da elevada proliferação e esfoliação de células cancerosas. Objetivo - Quantificar o DNA humano nas fezes de pacientes com câncer colorretal ou pólipos Métodos - Cinquenta pacientes com câncer colorretal, 26 pólipos e 53 com colonoscopia normal foram incluídas. DNA total e humano foram analisados a partir de fezes congeladas. Resultados - Maior concentração de hDNA nas fezes foi observada em pacientes com câncer colorretal em comparação com controles e pólipos. Pacientes com tumores localizados no cólon esquerdo apresentaram concentrações mais elevadas de hDNA. Não houve diferença entre pólipos e controles. Um nível de corte de 0.87ng/mL de DNA humano foi determinado para pacientes com câncer colorretal pela curva ROC, com sensibilidade de 66% e especificidade de 86,8%. Para pólipos o nível de corte foi de 0,41, a sensibilidade foi de 41% e a especificidade de 77,4%. Conclusão - Maior concentração de hDNA foi encontrada em pacientes com câncer colorretal. A quantificação de hDNA das fezes pode ser um método de rastreio do câncer colorretal.

Oral concentrated grape juice suppresses expression of NF-kappa B, TNF-α and iNOS in experimentally induced colorectal carcinogenesis in Wistar rats.

UNLABELLED: The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane (AOM) and expression of NF-kB, iNOS and TNF- α. METHODS: Forty male Wistar rats were divided into 7 groups: G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks before AOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juice without AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NF- kB, TNF- and iNOS was evaluated by qPCR. RESULTS: The number of ACF was higher in G2, and G4 presented a smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4 compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lower in G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed between TNF- α and NF-kB gene expression (p=0.002). In conclusion, the administration of 2% grape juice before AOM reduced the crypt multiplicity, attenuating carcinogenesis. Lower expression of NF-kB was observed in animals exposed to grape juice for a longer period of time, regardless of concentration.

HUMAN DNA QUANTIFICATION IN THE STOOLS OF PATIENTS WITH COLORECTAL CANCER.

BACKGROUND: Colorectal cancer is one of the main cause of cancer in the world. Colonoscopy is the best screen method, however the compliance is less than 50%. Quantification of human DNA (hDNA) in the feces may be a possible screen non-invasive method that is a consequence of the high proliferation and exfoliation of cancer cells. OBJECTIVE: To quantify the human DNA in the stools of patients with colorectal cancer or polyps. METHODS: Fifty patients with CRC, 26 polyps and 53 with normal colonoscopy were included. Total and human DNA were analyzed from the frozen stools. RESULTS: An increased concentration of hDNA in the stools was observed in colorectal cancer patients compared to controls and polyps. Tumors localized in the left side of the colon had higher concentrations of hDNA. There were no difference between polyps and controls. A cut off of 0.87 ng/mL of human DNA was determined for colorectal cancer patients by the ROC curve, with a sensitivity of 66% and a specificity of 86.8%. For polyps the cut off was 0.41, the sensitivity was 41% and the specificity 77.4%. CONCLUSION: A higher concentration of hDNA had been found in colorectal cancer patients The quantification of hDNA from the stools can be a trial method for the diagnosis of colorectal cancer.

RNA interference: a promising therapy for gastric cancer.

Gastric cancer (GC) remains a virtually incurable disease when metastatic and requires early screening tools for detection of early tumor stages. Therefore, finding effective strategies for prevention or recurrence of GC has become a major overall initiative. RNA-interference (RNAi) is an innovative technique that can significantly regulate the expression of oncogenes involved in gastric carcinogenesis, thus constituting a promising epigenetic approach to GC therapy. This review presents recent advances concerning the promising biomolecular mechanism of RNAi for GC treatment.

Establishment and partial characterization of an epirubicin-resistant gastric cancer cell line with upregulated ABCB1.

Multidrug resistance (MDR) is a major impediment to successful chemotherapy of gastric cancer. Our aim was to establish an epirubicin-resistant cell subline (AGS/EPI) and to elucidate the mechanisms involved in acquired EPI resistance. The AGS/EPI cell subline developed by exposing parental AGS cells to stepwise increasing concentrations of EPI demonstrated 2.52-fold resistance relative to the AGS cell line, and mRNA expression of the ATP-dependent drug-efflux pump P-glycoprotein (Pgp), more recently known as ABCB1 protein, was similarly upregulated. An AGS/EPI cell subline could thus be effectively established, and MDR mechanism of these cells was shown to be related to the overexpression of mRNA of the ABCB1 gene.

The influence of nutritional status and disease on adiponectin and TNF-ALFA levels in colorectal cancer patients / Influencia del estado nutritivo y la enfermedad sobre las concentraciones de adiponectina y TNF-ALPHA en pacientes con cáncer colorrectal

Background: The aim of this study was to evaluate the association between adiponectin and tumor necrosis factor-α (TNF-α) serum levels in colorectal cancer (CRC) patients and compare these levels to clinical stage and nutritional status. Methods: A total of 79 patients were enrolled in the study (39 with CRC and 40 in the control). Nutritional status was assessed by Patient-Generated Subjective Global Assessment (PG-SGA), body mass index (BMI), and phase angle (PhA). Adiponectin and TNF-α serum concentrations were determined using an enzyme-linked immunosorbent assay. Results: Serum adiponectin levels were higher among CRC patients (p = 0.001). TNF-α serum levels were not significantly different between the groups, but patients with stage III or IV CRC had higher levels of TNF-α than those with lower stage disease (p = 0.037). The three tools used for the assessment of nutritional status (BMI, PhA, and PG-SGA) demonstrated that patients with a more severe nutritional deficit had higher adipocytokine levels, although these differences were significant only to TNF- α, when distributed PhA in tertiles. Conclusions: Adiponectin levels were higher among CRC patients. Although TNF-α serum levels from CRC patients did not differ significantly to the control group, CRC patients with stage III or IV had higher levels compared to those with stage I and II tumors. Nutritional status, as determined by BMI, PhA, and PG-SGA, demonstrated that patients with a greatest nutritional deficit, had higher levels of adipocytokines; however, these differences were significant only for TNF-α, when distributed PhA in tertiles (AU)

Antecedentes: El propósito de este estudio fue evaluar la asociación entre las concentraciones séricas de adiponectina y de factor de necrosis tumoral-α (TNF-α) en paciente con cáncer colorrectal (CCR) y comparar estas concentraciones con el estadio clínico y el estado nutritivo. Métodos: Se reclutó a un total de 79 pacientes en el estudio (39 con CCR y 40 en el grupo control). Se evaluó el estado nutritivo mediante la Evaluación Global Subjetiva Generada por el Paciente (PG-SGA), el índice de masa corporal (IMC) y el ángulo de fase (AF). Se determinaron las concentraciones séricas de adiponectina y de TNF-α mediante un inmunoensayo de absorción ligado a enzima. Resultados: Las concentraciones séricas de adiponectina fueron superiores en los pacientes con CCR (p = 0,001). Las concentraciones séricas de TNF-α no fueron significativamente distintas entre los grupos pero los pacientes con CC en estadios III o IV tuvieron mayores concentraciones de TNF-α que aquellos con un menor estadio de la enfermedad (p = 0,037). Las tres herramientas empleadas para evaluar el estado nutritivo (IMC, AF y PG-SGA) demostraron que los pacientes con un déficit nutricional más pronunciado presentaban mayores concentraciones de adipocitocina, aunque algunas diferencias sólo fueron significativas para el TNF-α cuanto se distribuyó el AF en terciles. Conclusiones: Las concentraciones de adiponectina fueron superiores en pacientes con CCR. Aunque las concentraciones séricas de TNF-α de los pacientes con CCR no diferían significativamente de las del grupo control, los pacientes con CCR en estadios III o IV tuvieron concentraciones superiores en comparación con aquellos con tumores en estadios I y II. El estado nutritivo, determinado por IMC, AF y PG-SGA, demostró que los pacientes con un mayor déficit nutricional tenían concentraciones superiores de adipocitocinas; sin embargo, estas diferencias sólo fueron significativas para el TNF-α cuando el AF se distribuyó en terciles (AU)

Study of the polymorphisms of cyclooxygenase-2 (-765G>C) and 5-lipoxygenase (1708G>A) in patients with colorectal cancer.

Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. Genetic alterations have been associated with an increased risk of cancer and greater tumor aggressiveness. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) genes are important in cell cycle regulation, tumor growth and prostaglandin synthesis. The aim of the present study was to investigate the association between polymorphisms in the COX-2 and 5-LOX genes and the risk of CRC. A case-control study was conducted in patients with CRC matched for gender and age to a control group. DNA was extracted from peripheral leukocytes, and the polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and gene sequencing. A specific questionnaire was applied to evaluate smoking, excessive alcohol consumption, physical activity, non-steroidal anti-inflammatory drug use and meat, fiber and fat intake. A total of 185 patients with CRC and 146 controls were studied. The heterozygous GC genotype of the COX-2 gene polymorphism was the most common in the two groups (60.0% in CRC patients and 52.7% in controls). The CC genotype was associated with an increased risk of CRC (odds ratio, 3.63; 95% confidence interval, 1.31-10.1; P=0.013). The homozygous wild-type genotype of the 5-LOX gene polymorphism was detected in 72.4% of the CRC patients and in 71.2% of the control subjects. The homozygous mutant genotype (CC) of the COX-2 gene is an independent risk factor for CRC. No association was found between 5-LOX genotypes and CRC.

DNA methylation as an epigenetic biomarker in colorectal cancer.

Sporadic colorectal cancer (CRC) is a consequence of the accumulation of genetic and epigenetic alterations that result in the transformation of normal colonic epithelial cells to adenocarcinomas. Studies have indicated that a common event in the tumorigenesis of CRC is the association of global hypomethylation with discrete hypermethylation at the promoter regions of specific genes that are involved in cell cycle regulation, DNA repair, apoptosis, angiogenesis, adhesion and invasion. The present study aimed to investigate the epigenetic changes (DNA methylation) in 24 candidate genes in CRC. A total of 10 candidate hypermethylated (HM) and unmethylated (UM) genes were identified that may be useful epigenetic markers for non-invasive CRC screening. The five genes that had the highest average UM percentages in the control group were MLH1 (71.7%), DKK2 (69.6%), CDKN2A (68.4%), APC (67.5%) and hsa-mir-342 (67.4%). RUNX3 (58.9%), PCDH10 (55.5%), SFRP5 (52.1%), IGF2 (50.4%) and Hnf1b (50.0%) were the five genes with the highest average HM percentages in the test group. In summary, the present preliminary study identified the methylation profiles of normal and cancerous colonic epithelial tissues, and provided the groundwork for future large-scale methylation studies.

What are the most effective methods for assessment of nutritional status in outpatients with gastric and colorectal cancer?

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 (PGSGA)]. 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.

Objetivo: Evaluar los métodos para la identificación del riesgo nutricional y del estado nutricional en pacientes ambulatorios con cáncer colorrectal (CCR) y cáncer gástrico (CG) y comparar los resultados con los obtenidos por los pacientes ya tratados por estos cánceres. Métodos: Se realizó un estudio transversal en 137 pacientes: el grupo 1 (n = 75) comprendía pacientes con CG o CCR y el grupo 2 (n = 62) comprendía pacientes tras el tratamiento de CG o CCR en seguimiento y que estaban libres de tumor por un periodo mayor de 3 meses. Se evaluó el estado nutricional de estos pacientes usando métodos objetivos [índice de masa corporal (IMC), el ángulo de fase y la albúmina sérica]; herramientas de cribado nutricional [Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST), Nutritional Risk Index (NRI)] y una evaluación subjetiva [Evaluación Global Subjetiva Generada por el Paciente (EGS-GP)]. La sensibilidad y especificidad de cada método se calcularon con relación a la EGS-GP, que se empleó como prueba de referencia. Resultados: 137 pacientes participaron en el estudio. Los pacientes con cáncer en estadio IV fueron más frecuentes en el grupo 1. No hubo diferencias en el IMC entre los grupos (p = 0,67). El análisis de la asociación entre los métodos de evaluación nutricional y la EGSGP mostró que las herramientas de cribado nutricional proporcionaban resultados más significativos (p < 0,05) que los métodos objetivos en ambos grupos. La EGS-GP detectó la mayor proporción de pacientes desnutridos en el grupo 1. Las herramientas de cribado nutricional MUST, NRI y MST eran más sensibles que los métodos objetivos. La medición del ángulo de fase fue el método objetivo más sensible en el grupo 1. Conclusión: Las herramientas de cribado nutricional mostraron la mejor asociación con la EGS-GP y también fueron más sensibles que los métodos objetivos. Los resultados sugieren el uso de la combinación de MUST y EGSGP en pacientes con cáncer antes y después del tratamiento.

What are the most effective methods for assessment of nutritional statusin outpatients with gastric and colorectal cancer? / ¿Cuáles son los métodos más eficaces de valoración del estado nutricional en pacientes ambulatorios con cáncer gástrico y colorrectal?

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 (PGSGA)]. 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 (AU)

Objetivo: Evaluar los métodos para la identificación del riesgo nutricional y del estado nutricional en pacientes ambulatorios con cáncer colorrectal (CCR) y cáncer gástrico (CG) y comparar los resultados con los obtenidos por los pacientes ya tratados por estos cánceres. Métodos: Se realizó un estudio transversal en 137 pacientes: el grupo 1 (n = 75) comprendía pacientes con CG o CCR y el grupo 2 (n = 62) comprendía pacientes tras el tratamiento de CG o CCR en seguimiento y que estaban libres de tumor por un periodo mayor de 3 meses. Se evaluó el estado nutricional de estos pacientes usando métodos objetivos [índice de masa corporal (IMC), el ángulo de fase y la albúmina sérica]; herramientas de cribado nutricional [Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST), Nutritional Risk Index (NRI)] y una evaluación subjetiva [Evaluación Global Subjetiva Generada por el Paciente (EGS-GP)]. La sensibilidad y especificidad de cada método se calcularon con relación a la EGS-GP, que se empleó como prueba de referencia. Resultados: 137 pacientes participaron en el estudio. Los pacientes con cáncer en estadio IV fueron más frecuentes en el grupo 1. No hubo diferencias en el IMC entre los grupos (p = 0,67). El análisis de la asociación entre los métodos de evaluación nutricional y la EGSGP mostró que las herramientas de cribado nutricional proporcionaban resultados más significativos (p < 0,05) que los métodos objetivos en ambos grupos. La EGS-GP detectó (..) (AU)