Publications by authors named "Nora Manoukian Forones"

64 Publications

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 2): UPDATE ON TREATMENT.

Arq Bras Cir Dig 2021 14;34(1):e1563. Epub 2021 May 14.

Hospital das Clinicas HCFMUSP, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil.

Background: : The II Brazilian Consensus on Gastric Cancer of the Brazilian Gastric Cancer Association BGCA (Part 1) was recently published. On this occasion, countless specialists working in the treatment of this disease expressed their opinion in the face of the statements presented.

Aim: : To present the BGCA Guidelines (Part 2) regarding indications for surgical treatment, operative techniques, extension of resection and multimodal treatment.

Methods: To formulate these guidelines, the authors carried out an extensive and current review regarding each declaration present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases initially with the following descriptors: gastric cancer, gastrectomy, lymphadenectomy, multimodal treatment. In addition, each statement was classified according to the level of evidence and degree of recommendation.

Results: : Of the 43 statements present in this study, 11 (25,6%) were classified with level of evidence A, 20 (46,5%) B and 12 (27,9%) C. Regarding the degree of recommendation, 18 (41,9%) statements obtained grade of recommendation 1, 14 (32,6%) 2a, 10 (23,3%) 2b e one (2,3%) 3.

Conclusion: : The guidelines complement of the guidelines presented here allows surgeons and oncologists who work to combat gastric cancer to offer the best possible treatment, according to the local conditions available.
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http://dx.doi.org/10.1590/0102-672020210001e1563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121052PMC
May 2021

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

Arq Gastroenterol 2021 Jan-Mar;58(1):55-60

Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP-EPM), São Paulo, SP, Brasil.

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.
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http://dx.doi.org/10.1590/S0004-2803.202100000-10DOI Listing
April 2021

NONINVASIVE BREATH TESTS FOR DIAGNOSIS OF SIBO AND LACTOSE INTOLERANCE IN PATIENTS ON CHEMOTHERAPY TREATMENT FOR COLORECTAL AND GASTRIC CÂNCER.

Arq Gastroenterol 2021 Jan-Mar;58(1):26-31

Universidade Federal de São Paulo, Disciplina de Gastroenterologia, São Paulo, SP, Brasil.

Background: Worldwide, colorectal cancer (CRC) and gastric cancer (GC) are the third and the fifth most prevalent, respectively. Diarrhea is a common symptom in patients on chemotherapy or radiotherapy treatment and can reduce treatment tolerance. Surgical resections and chemotherapy change the intestinal microbiota that can lead to lactose intolerance, small intestinal bacterial overgrowth (SIBO).

Objective: The aim of the study was to evaluate the frequency of diarrhea in patients with CRC and GC on chemotherapy with SIBO or intolerance of lactose.

Methods: This is a descriptive and observational study with patients of both sexes, over 18 years old, in treatment in the Gastro-Oncology outpatient clinic of the Federal University of São Paulo. Patients with a confirmed diagnosis of CRC or GC during chemotherapy treatment were included. To detect bacterial overgrowth and lactose intolerance, breath hydrogen test with lactulose and lactose was done. Number and aspects of the evacuations and toxicity degree were collected. For the nutritional assessment, weight and height were performed to calculate the BMI. and the Patient Generated Subjective Global Assessment (PG-SGA).

Results: A total of 33 patients were included, 29 with CRC and 3 with GC. Most of them were male (57.57%), mean age of 60.03±10.01 years and in chemotherapy with fluoropyrimidine and oxaliplatin (54.5%). Diarrhea was present in 57.6% and 30.3% had toxicity grade 2. According to the BMI, 78.9% were eutrophics, obese or overweight, but according to PG-SGA, 84.9% had moderate or severe nutritional risk grade. Between patients, 45% had lactose intolerance and 9% SIBO. Diarrhea grade 2-3 was observed in 66.6% of patients with SIBO and 66.7% of that with lactose intolerance. No statistical difference was observed between patients with SIBO or lactose intolerance and grade of diarrhea.

Conclusion: Diarrhea was a frequent symptom in chemotherapy patients with gastric or colorectal cancer independent of the presence of SIBO or lactose intolerance. Surgery and chemotherapy treatment impacted in the intestinal habit of patients. Diagnosis of other causes of diarrhea may contribute to a better tolerance to treatment and quality of life.
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http://dx.doi.org/10.1590/S0004-2803.202100000-06DOI Listing
April 2021

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 1): AN UPDATE ON DIAGNOSIS, STAGING, ENDOSCOPIC TREATMENT AND FOLLOW-UP.

Arq Bras Cir Dig 2020 18;33(3):e1535. Epub 2020 Dec 18.

Hospital das Clinicas HCFMUSP, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil.

Background: The II Brazilian Consensus on Gastric Cancer by the Brazilian Gastric Cancer Association (ABCG) was recently published. On this occasion, several experts in gastric cancer expressed their opinion before the statements presented.

Aim: To present the ABCG Guidelines (part 1) regarding the diagnosis, staging, endoscopic treatment and follow-up of gastric cancer patients.

Methods: To forge these Guidelines, the authors carried out an extensive and current review regarding each statement present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases with the following descriptors: gastric cancer, staging, endoscopic treatment and follow-up. In addition, each statement was classified according to the level of evidence and degree of recommendation.

Results: Of the 24 statements, two (8.3%) were classified with level of evidence A, 11 (45.8%) with B and 11 (45.8%) with C. As for the degree of recommendation, six (25%) statements obtained grade of recommendation 1, nine (37.5%) recommendation 2a, six (25%) 2b and three (12.5%) grade 3.

Conclusion: The guidelines presented here are intended to assist professionals working in the fight against gastric cancer with relevant and current information, granting them to be applied in the daily medical practice.
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http://dx.doi.org/10.1590/0102-672020200003e1535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747489PMC
December 2020

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria.

Asian Pac J Cancer Prev 2020 Feb 1;21(2):343-348. Epub 2020 Feb 1.

Department of Pathology, Federal University of Sao Paulo, Sao Paulo, Brazil.

Colorectal cancer (CRC) is one of the most frequent neoplasms worldwide, and up to 15% have a family history. Lynch syndrome (LS) is a hereditary cause of CRC and gastric (GC). Individuals with LS have mutations in mismatch genes repair. p53, cyclin D1, β-catenin, APC and c-myc proteins are involved in the cell cycle and carcinogenesis.

Objective: To study the expression of p53, Cyclin D1, β-catenin, APC and c-myc proteins in patients with CRC and GC with at least one of the Bethesda positive criteria. Compare the expression of these proteins with the presence or absence of expression of the DNA repair proteins.

Patients And Methods: We included 70 individuals with CRC or GC with at least one of the Bethesda positive criteria. Protein expression of MLH1, MSH2, MSH6, PMS2, p53, cyclin D1, β-catenin, APC and c-myc were analized by immunohistochemistry tumours tissues.

Results: Deficient expression of MLH1, MSH2, MSH6 and PMS2 were respectively 38.7%; 17.7%; 26.22% and 48.38%. We found a negative association between deficiency of PMS2 and age, and positive association between PMS2 deficiency and APC positive. The positive imunoexpression of APC increases by 4 times the chance of having deficiency of PMS2.

Conclusions: Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.
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http://dx.doi.org/10.31557/APJCP.2020.21.2.343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332149PMC
February 2020

Label-free peptide quantification coupled with in silico mapping of proteases for identification of potential serum biomarkers in gastric adenocarcinoma patients.

Clin Biochem 2020 May 22;79:61-69. Epub 2020 Feb 22.

Department of Medicine, Division of Gastroenterology, Oncology Group, Federal University of São Paulo, São Paulo, SP, Brazil.

Objectives: We aimed to identify serum level variations in protein-derived peptides between patients diagnosed with gastric adenocarcinoma (GAC) and non-cancer persons (control) to detect the activity changes of proteases and explore the auxiliary diagnostic value in the context of GAC physiopathology.

Methods: The label-free quantitative peptidome approach was applied to identify variants in serum levels of peptides that can differentiate GAC patients from the control group. Peptide sequences were submitted against Proteasix tool predicting proteases potentially involved in their generation. The activity change of proteases was subsequently estimated based on the peptides with significantly altered relative abundance. In turn, activity change prediction of proteases was correlated with relevant protease expression data from the literature.

Results: A total of 191 peptide sequences generated by the cleavage of 36 precursor proteins were identified. Using the label-free quantification approach, 33 peptides were differentially quantified (adjusted fold change ≥ 1.5 and p-value < 0.05) in which 19 were up-regulated and 14 were down-regulated in GAC samples. Of these peptides, fibrinopeptide A was significantly decreased and its phosphorylated form ADpSGEGDFLAEGGGVR was upregulated in GAC samples. Activity change prediction yielded 10 proteases including 6 Matrix Metalloproteinases (MMPs), Thrombin, Plasmin, and kallikreins 4 and 14. Among predicted proteases in our analysis, MMP-7 was presented as a more promising biomarker associated with useful assays of clinical practice for GAC diagnosis.

Conclusion: Our experimental results demonstrate that the serum levels of peptides were significantly differentiated in GAC physiopathology. The hypotheses built on protease regulation could be used for further investigations to measure proteases and their activity levels that have been poorly studied for GAC diagnosis.
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http://dx.doi.org/10.1016/j.clinbiochem.2020.02.010DOI Listing
May 2020

STUDY OF LIPID BIOMARKERS OF PATIENTS WITH POLYPS AND COLORECTAL CÂNCER.

Arq Gastroenterol 2019 Oct-Dec;56(4):399-404

Universidade Federal de São Paulo, Disciplina de Gastroenterologia, Departamento de Medicina, São Paulo, SP, Brasil.

Background: Colorectal cancer (CRC) is one of the leading causes of cancer worldwide. Early diagnostic methods using serum biomarkers are required. The study of omics, most recently lipidomics, has the purpose of analyzing lipids for a better understanding of human lipidoma. The evolution of mass spectrometry methods, such as MALDI-MS technology, has 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 lipid profile of patients with colorectal cancer and polyps.

Methods: Patients with stage I-III CRC, adenomatous polyps and individuals with normal colonoscopy were selected. All patients underwent peripheral blood collection for lipid extraction. The samples were analyzed by MALDI-MS technique for lipid identification.

Statistical Analysis: Univariate and multivariate (principal component analysis [PCA] and discriminant analysis by partial least squares [PLS-DA]) analyses workflows were applied to the dataset, using MetaboAnalyst 3.0 software. The ions were identified according to the class of lipids using the online database Lipid Maps (http://www.lipidmaps.org).

Results: We included 88 individuals, 40 with CRC, 12 with polyps and 32 controls. Boxplot analysis showed eight VIP ions in the three groups. Differences were observed between the cancer and control groups, as well as between cancer and polyp, but not between polyps and control. The polyketide (810.1) was the lipid represented in cancer and overrepresented in polyp and control. Among the patients with CRC we observed differences between lipids with lymph node invasion (N1-2) compared to those without lymph node invasion (N).

Conclusion: Possible lipid biomarkers were identified among cancer patients compared to control and polyp groups. The polyketide lipid (810.1) was the best biomarker to differentiate the cancer group from control and polyp. We found no difference between the biomarkers in the polyp group in relation to the control.
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http://dx.doi.org/10.1590/S0004-2803.201900000-80DOI Listing
January 2020

High-resolution melting for detecting mutations in colorectal cancer.

Biomed Rep 2019 Dec 7;11(6):269-273. Epub 2019 Nov 7.

Gastroenterology Division, Department of Medicine, Gastrointestinal Oncology Group, Universidade Federal de Sao Paulo, Sao Paulo CEP 04023900, Brazil.

Colorectal cancer is a leading cause of cancer that may metastasize. 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 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.
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http://dx.doi.org/10.3892/br.2019.1254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873417PMC
December 2019

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

Asian Pac J Cancer Prev 2019 Oct 1;20(10):2929-2934. Epub 2019 Oct 1.

Oncology Group, Gastroenterology Division, Medicine Department, Universidade Federal de Sao Paulo, São Paulo, Brazil.

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.
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http://dx.doi.org/10.31557/APJCP.2019.20.10.2929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982689PMC
October 2019

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

Arq Gastroenterol 2019 Aug 13;56(2):172-177. Epub 2019 Aug 13.

Universidade Federal de São Paulo (UNIFESP), Setor de Oncologia, Disciplina de Gastroenterologia Clínica, Departamento de Medicina, São Paulo, SP, Brasil.

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.
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http://dx.doi.org/10.1590/S0004-2803.201900000-34DOI Listing
August 2019

A snapshot of current genetic testing practice in Lynch syndrome: The results of a representative survey of 33 Latin American existing centres/registries.

Eur J Cancer 2019 09 20;119:112-121. Epub 2019 Aug 20.

Hospital de Especialidades Eugenio Espejo, Subproceso de Anatomía Patológica, Área de Genética Clínica, Quito, Ecuador.

We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica). In total, 87% (26/30) of the participating centres/registries belonging to the nine countries are performing genetic testing. Overall, 1352 suspected families were sequenced. Pathogenic variants were identified in 34% of the families, with slightly differing distribution of variants between females and males. Path_MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path_MSH2 were identified in 37% of females and males, followed by path_PMS2 in 11% of females and 8% of males, path_MSH6 in 13% of females and 3% of males (p < 0.001) and path_EPCAM in 0.3% of females and 2% of males. In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for LS. LS screening is inconsistently applied within Latin America healthcare systems because of structural differences in the healthcare systems between the countries.
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http://dx.doi.org/10.1016/j.ejca.2019.07.017DOI Listing
September 2019

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

BMC Cancer 2019 Jun 29;19(1):644. Epub 2019 Jun 29.

Department of Medicine. Gastroenterology Division. Oncology Group, Universidade Federal de São Paulo - SP. Brazil, R Botucatu 740, 2° andar CEP 04023900, Vila Clementino, São Paulo, Brazil.

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 cm in men and <  80.1 cm 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.
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http://dx.doi.org/10.1186/s12885-019-5837-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599287PMC
June 2019

Effects of Grape Juice in Superoxide Dismutase and Catalase in Colorectal Cancer Carcinogenesis Induced by Azoxymethane

Asian Pac J Cancer Prev 2018 Oct 26;19(10):2839-2844. Epub 2018 Oct 26.

Department of Medicine – Discipline of Gastroenterology – Universidade Federal de São Paulo – Escola Paulista de Medicina, UNIFESP/EPM, SP, Brazil. Email:

Background: The intestinal mucosa is commonly exposed to oxidant nutrients and carcinogens, which can lead to the generation of free radicals. The antioxidants present in the diet assume great importance as possible protective agents, reducing the oxidative damage. In this way, we evaluated the antioxidant action of grape juice on preneoplastic lesions induced by azoxymethane (AOM) in Wistar rats. Methods: The colorectal carcinogenesis was induced by two intraperitoneal injections of 15mg/kg of AOM in Wistar rats. The animals were divided in 7 groups and treated with 1 and 2% concentrations of grape juice before and after carcinogen administration. After euthanasia, the expression of antioxidant enzymes catalase (CAT), copper-zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD) CAT, SOD1 and SOD2 were evaluated by immunohistochemistry. Results: AOM decreased the expression of CAT and Mn-SOD enzymes, but not for Cu/Zn-SOD. We observed an increase expression of CAT and Mn-SOD after grape juice administration in some concentrations according to the time of administration of the grape juice before the carcinogen or just after the carcinogen. Conclusion: Our results suggest an independent action of each enzyme and a possible antioxidant action of the grape juice components in the diet being able to balance the body to neutralize the superoxide radicals and not leave them in the cell-damaging form.
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http://dx.doi.org/10.22034/APJCP.2018.19.10.2839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291046PMC
October 2018

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America.

Int J Cancer 2019 07 5;145(2):318-326. Epub 2018 Dec 5.

AC Camargo Cancer Center, Sao Paulo, Brazil.

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%-80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.
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http://dx.doi.org/10.1002/ijc.31920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587543PMC
July 2019

Heparan Sulfate Proteoglycans in Human Colorectal Cancer.

Anal Cell Pathol (Amst) 2018 20;2018:8389595. Epub 2018 Jun 20.

Disciplina de Biologia Molecular, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio, 100 4° Andar, Vila Clementino, São Paulo, SP, Brazil.

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.
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http://dx.doi.org/10.1155/2018/8389595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031075PMC
October 2018

Analysis of the Lipid Profile in Patients with Colorectal Cancer in Advanced Stages

Asian Pac J Cancer Prev 2018 May 26;19(5):1287-1293. Epub 2018 May 26.

Department of Medicine, Gastroenterology Division, Federal University of Sao Paulo, Brazil. Email:

Backgrounds: Colorectal (CRC) is one of the main cause of cancer worldwide. The search for noninvasive markers for diagnosis and monitoring as the use of analytical technologies such as mass spectrometry (MS), which allowed the search for lipid metabolites as candidates for probable biomarkers are needed. Objective and Methods: The objective was to establish the lipid profile of patients with locally advanced, unresectable or metastatic CRC. Peripheral blood was collected from patients with CRC and controls 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. Results: 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 1,000 permutations a p <0.001. The classes of lipids found were sphingolipids, glycerophospholipids and policetidis. The strength of the association between the peak intensities of these lipids and the presence of CRC make these metabolites candidates for possible biomarkers. The 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 policetidis (m / z = 876.20796) and glycerophospholipid (m / z = 1031.54773).
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http://dx.doi.org/10.22034/APJCP.2018.19.5.1287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031810PMC
May 2018

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

Asian Pac J Cancer Prev 2018 May 26;19(5):1237-1242. Epub 2018 May 26.

Department of Medicine, Gastroenterology Division, Federal University of Sao Paulo, Brazil.

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.
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http://dx.doi.org/10.22034/APJCP.2018.19.5.1237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031827PMC
May 2018

A randomised phase II study of chemoradiotherapy with or without nimotuzumab in locally advanced oesophageal cancer: NICE trial.

Eur J Cancer 2018 01 24;88:21-30. Epub 2017 Nov 24.

Hospital Erasto Gaertner, Curitiba, Brazil. Electronic address:

Purpose: Chemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR).

Patients And Methods: Untreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated.

Results: We enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44-1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm.

Conclusion: Combined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL.

Clinical Trials: Identification number: EF024-201; Trial registry: NCT01249352.
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http://dx.doi.org/10.1016/j.ejca.2017.10.005DOI Listing
January 2018

Quality Oncology Practice Initiative Can Guide and Improve Oncology Providers' Training in Brazil.

J Glob Oncol 2017 Jun 21;3(3):189-193. Epub 2016 Sep 21.

, , , , , , , and , Universidade Federal de São Paulo, São Paulo, Brazil; and , University of Notre Dame, Notre Dame, IN.

Purpose: It has become crucial to translate scientific findings and to find ways by which to mobilize local resources to improve the quality and accessibility of cancer care in developing countries. This study seeks to provide insight into challenge through examining differences in clinician documentation of patients with cancer treated at a Brazilian Public University Hospital.

Methods: ASCO Quality Oncology Practice Initiative (QOPI) measures were used to examine the care provided in the departments of breast, colorectal, lymphoma, gynecology, and lung cancers. For this study, data from a representative sample of patients receiving chemotherapy in the previous month were extracted and quality of cancer care indicators examined.

Results: Certain elements of medical care were consistently and appropriately documented, including cancer diagnosis and stage, chemotherapy planning, administration, and summary. In general, considering the specific cancer management measures, patients received recommended care in accordance with recognized guidelines. Despite this, a number of important gaps in care were identified, including the assessment and treatment of pain, documentation of chemotherapy intention, symptom and toxicity management, patients' psychosocial status, and provision of a treatment summary at care completion.

Conclusion: These findings are encouraging in terms of adherence to core treatment guidelines in cancer care in Brazil. However, results suggest important opportunities for improving care across a number of domains, many of which represent a challenge throughout both developing and developed countries. This study may also provide preliminary guidance for enhancing educational and training programs for professionals and students alike, to implement high-quality, comprehensive cancer care.
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http://dx.doi.org/10.1200/JGO.2016.006148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493225PMC
June 2017

Genetic polymorphisms of vitamin D metabolism genes and serum level of vitamin D in colorectal cancer.

Int J Biol Markers 2017 Oct 31;32(4):e441-e446. Epub 2017 Oct 31.

Oncology Division, Gastroenterology Department, Federal University of São Paulo, São Paulo - Brazil.

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)D3 (circulating form) and 1,25(OH)2D3 (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; however, the percentage of those with deficient vitamin D was higher in patients with cancer. The active form of the vitamin D was higher in CRC patients. VDR, CYP27B1 and CYP24A1 polymorphic genotypes had no influence on serum levels of circulating vitamin D. The correlation between circulating and active vitamin D forms was lower among patients with CRC, regardless of the presence or absence of any genetic polymorphism. The mean serum levels of active vitamin D were higher among patients with polymorphic genotype variants of Apa1 or Bsm1.

Conclusions: CRC patients had a higher frequence of insufficient vitamin D and a higher concentration of active vitamin D. These concentration were higher between patients with polymorphic genotypes variants of ApaI and BsmI, CYP24A1 and CYP27B1. Polymorphic genotypes cause a lower correlation between the forms of vitamin D.
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http://dx.doi.org/10.5301/ijbm.5000282DOI Listing
October 2017

Association Between Nutrition Status and Survival in Elderly Patients With Colorectal Cancer.

Nutr Clin Pract 2017 Oct 23;32(5):658-663. Epub 2017 May 23.

1 Department of Gastrointestinal Oncology, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.

Background: Aging patients with cancer have a higher risk of mortality and treatment-associated morbidity than younger patients. Nutrition status may play an important role in cancer mortality. We aimed to evaluate the survival time of elderly patients with colorectal cancer and its association with body mass index (BMI), the patient-generated subjective global assessment (PG-SGA), and phase angle (PA).

Materials And Methods: BMI, PG-SGA, and PA were determined for all patients (n = 250) at first assessment.

Results: Seventy-one (28.4%) patients were in active oncologic treatment (group 1) and 179 (71.6%) were in remission (group 2). At the time of the analysis, 73 (29.2%) patients had died and 177 (70.8%) were censored. The mean (standard deviation) age was 70.9 (7.49) years; 17.2% were undernourished, 56% normal weight, and 26.8% were overweight. According to the PG-SGA, 35.2% of patients needed some nutrition intervention and 4.4% needed it urgently. The mean PA was 4.94 ± 1°. PG-SGA, tumor stage, and PA differed significantly ( P < .001) between the groups; BMI did not ( P = .459). Severe malnutrition (PG-SGA C), compared with PG-SGA A, was associated with a relative hazard of death of 12.04 (95% confidence interval [CI], 3.43-42.19, P < .001). PA >5° was associated with better prognosis: a relative hazard of 0.456 (95% CI, 0.263-0.792; P < .005).

Conclusion: Among elderly patients with colorectal cancer, PA and PG-SGA were prognosis factors. PA >5° was associated with best survival and PG-SGA C with worst survival.
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http://dx.doi.org/10.1177/0884533617706894DOI Listing
October 2017

Cachexia Stage, Patient-Generated Subjective Global Assessment, Phase Angle, and Handgrip Strength in Patients with Gastrointestinal Cancer.

Nutr Cancer 2017 Jul 19;69(5):772-779. Epub 2017 May 19.

c Division of Gastroenterology, Department of Medicine , Universidade Federal de Sao Paulo , Sao Paulo , Brazil.

The aim of this study was to correlate patients with gastrointestinal cancer, classified according to different stages of cancer cachexia (SCC) as proposed by Fearon, with nutritional assessment tools such as PG-SGA, phase angle (PA), and handgrip strength. One hundred one patients with a mean age of 61.8 ± 12.8 yr, with 58.4% being men were included. 32.6% were malnourished according to the body mass index (BMI). A severe or moderate malnutrition had been diagnosed in 63.3% when assessed using the PG-SGA, 60.4% had decreased handgrip strength, and 57.4% had lower grades of PA. Among the patients in the study, 26% did not have cachexia, 11% had precachexia, 56% cachexia, and 8% refractory cachexia. The PG-SGA, PA, and handgrip strength were associated with cachexia (P ≤ 0.001). An increased risk of death was found in patients with cachexia [RR: 9.1; confidence interval (CI) 95%: 0.1-90.2, P = 0.039], refractory cachexia (RR: 69.4, CI 95%: 4.5-1073.8, P = 0.002), and increased serum C-reactive protein (CRP) levels (P < 0.001). In conclusion, most of the patients with digestive system cancer had cachexia or refractory cachexia in the first nutritional assessment. Nutritional risk, as determined by PG-SGA, was correlated with PA and handgrip strength. High CRP levels, cachexia, and refractory cachexia were prognostic factors for cancer patients.
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http://dx.doi.org/10.1080/01635581.2017.1321130DOI Listing
July 2017

Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group.

Ecancermedicalscience 2017 26;11:716. Epub 2017 Jan 26.

Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Departamento de Radiologia e Oncologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brasil.

Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.
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http://dx.doi.org/10.3332/ecancer.2017.716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295846PMC
January 2017

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

Int J Biol Markers 2017 May 4;32(2):e224-e230. Epub 2017 May 4.

Oncology Division, Gastroenterology Department, Universidade Federal de São Paulo, São Paulo - Brazil.

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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http://dx.doi.org/10.5301/jbm.5000248DOI Listing
May 2017

HER2 EXPRESSION AS A PROGNOSTIC FACTOR IN METASTATIC GASTRIC CANCER.

Arq Gastroenterol 2016 Apr-Jun;53(2):62-7

Disciplina de Gastroenterologia, Universidade Federal de São Paulo, SP, Brasil., Universidade Federal de São Paulo, Universidade Federal de São Paulo, SP , Brazil.

Background: - Human epidermal growth factor receptor 2 (EGFR2/HER2/ErbB2) is a transmembrane receptor that stimulates cell proliferation when activated. The correlation of HER2 expression with prognosis has been studied in many cancer types. However, its relationship with survival of patients with metastatic gastric cancer remains unknown. Moreover, there is a lack of information on this issue in a Brazilian population.

Objective: - To assess the proportion of patients whose tumor cells express HER2 and correlate this with clinical characteristics as well as treatment outcomes.

Methods: - This was a retrospective study. We included adult patients with metastatic gastric cancer treated at an University Hospital between 2011 and 2015. Patients did not receive anti-HER2 therapy. Receptor expression was evaluated by immunohistochemistry. Survival risk factors were assessed individually with univariate Cox regression, and a P value <0.05 was considered statistically significant.

Results: - Forty-nine patients were included in this study. However, only 32 had samples assessed for HER2 expression. Five (16%) patients were positive. Among HER2-negative patients, the average age was 54 years, 44% received a treatment protocol with three drugs, 70% had a performance status score 0-1, and 41% had well or moderately differentiated histology. Among HER2-positive patients, the average age was 58 years, 40% received three drugs, 100% had a performance status score 0-1, and 67% had well or moderately differentiated histology. Response rate was evaluated in 28 cases, and there was no difference between the groups (HER2-negative 52% vs. HER2-positive 40%; P=0.62). Survival outcomes were numerically worse among HER2-positive patients. Median progression-free survival was 8.3 months for HER2-positive patients and 10.6 months for HER2-negative patients (HR 1.61, 95% CI: 0.59-4.38); median overall survival was 14.8 months and 16.9 months for HER2-positive and HER2-negative patients, respectively (HR 1.52, 95% CI: 0.50-4.66).

Conclusion: - HER2 overexpression in metastatic gastric cancer patients may be a predictor of poor prognosis and further validation is warranted.
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http://dx.doi.org/10.1590/S0004-28032016000200003DOI Listing
February 2017

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

Arq Gastroenterol 2015 Dec;52(4):293-8

Universidade Federal de São Paulo, São Paulo, SP, Brasil.

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.
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http://dx.doi.org/10.1590/S0004-28032015000400008DOI Listing
December 2015

Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

Future Oncol 2016 03 3;12(6):839-54. Epub 2016 Feb 3.

Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal.

In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.
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http://dx.doi.org/10.2217/fon.15.348DOI Listing
March 2016

MMR deficiency may lead to a high immunogenicity and then an improvement in anti-PD-1 efficacy for metastatic colorectal cancer.

Immunotherapy 2015 16;7(11):1133-4. Epub 2015 Nov 16.

Department of Biomedical Sciences & Medicine, University of Algarve, Faro, Portugal.

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http://dx.doi.org/10.2217/imt.15.84DOI Listing
September 2016

Chemopreventive activity of grape juice concentrate (G8000TM) on rat colon carcinogenesis induced by azoxymethane.

Environ Toxicol Pharmacol 2015 Nov 28;40(3):870-5. Epub 2015 Sep 28.

Oncology Division, Medicine Department, Universidade Federal de São Paulo UNIFESP/EPM, SP, Brazil.

Colorectal cancer is the third most common cancer worldwide in both sexes, with similar geographic patterns between genders. This neoplasm has good prognosis if the disease is diagnosed at early stages. The aim of this study was to evaluate the effect of red grape juice on the expression of COX-2 and Ki-67 expression following colon carcinogenesis induced by azoxymethane (AOM). Thirty-five rats were randomly distributed into seven groups (n=5 per group): G1: SHAM or negative control received only saline; G2 (positive control): animals received 15 mg/kg AOM; G3: animals received 1% red grape juice 2 weeks before the administration of AOM; G4: animals received 2% red grape juice 2 weeks before the administration of AOM; G5: animals received 1% red grape juice 4 weeks after the last administration of AOM; G6: animals received 2% red grape juice 4 weeks after the last administration of AOM; G7: animals received only 2% red grape juice. COX-2 mRNA expression was reduced in animals treated with 1% red grape juice before AOM induction or 2% red grape juice after AOM induction. COX-2 immunoexpression was also reduced to groups treated with red grape juice at 1% before and after AOM induction or 2% red grape juice after AOM induction. Decreased immunoexpression of Ki-67 positive cells was observed in animals treated with 1% grape juice before AOM-treated animals. Taken together, grape juice concentrate is able to exert some chemopreventive activity on rat colon carcinogenesis.
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http://dx.doi.org/10.1016/j.etap.2015.09.012DOI Listing
November 2015

Treating operable patients with gastric cancer: Macdonald's protocol versus adjuvant chemotherapy.

Future Oncol 2015 ;11(16):2247-9

Department of Biomedical Sciences & Medicine, University of Algarve, Campus de Gambelas, Edifício 7, ala nascente, 3o. andar, 8005 - 139, Faro, Portugal.

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http://dx.doi.org/10.2217/fon.15.141DOI Listing
May 2016