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1.
Int J Cancer ; 136(4): 880-93, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24947433

RESUMO

ABO blood serotype A is known to be associated with risk of gastric cancer (GC), but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and genes which are involved in Lewis antigen formation [and in Helicobacter pylori (H. pylori) binding and pathogenicity] may be related to GC risk in a European population. The authors conducted an investigation of 32 variants at ABO and FUT1-7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested within the EPIC cohort (the EPIC-Eurgast study). Four variants (including rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio=1.84, 95%CI=1.20-2.80) were associated with diffuse-type GC; however, conditional models with other ABO variants indicated that the associations were largely due to allelic blood group A. One variant in FUT5 was also associated with diffuse-type GC, and four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal-type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated with H. pylori infection status in controls, and two of these (in FUT3 and FUT6) were weakly associated with intestinal-type GC risk. None of the individual variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however, after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)] were significantly associated with diffuse- and intestinal-type GC, respectively. Replication and functional studies are therefore recommended to clarify the role of ABO and FUT alleles in H. pylori infection and subtype-specific gastric carcinogenesis.


Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Adenocarcinoma/genética , Fucosiltransferases/genética , Neoplasias Gástricas/genética , Adenocarcinoma/enzimologia , Idoso , Estudos de Casos e Controles , Europa (Continente) , Feminino , Frequência do Gene , Estudos de Associação Genética , Loci Gênicos , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Risco , Neoplasias Gástricas/enzimologia
2.
PLoS One ; 8(5): e64441, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23691218

RESUMO

The protein deleted in malignant brain tumors (DMBT1) and the trefoil factor (TFF) proteins have all been proposed to have roles in epithelial cell growth and cell differentiation and shown to be up regulated in inflammatory bowel diseases. A panel of monoclonal antibodies was raised against human DMBT1(gp340). Analysis of lung washings and colon tissue extracts by Western blotting in the unreduced state, two antibodies (Hyb213-1 and Hyb213-6) reacted with a double band of 290 kDa in lung lavage. Hyb213-6, in addition, reacted against a double band of 270 kDa in colon extract while Hyb213-1 showed no reaction. Hyb213-6 showed strong cytoplasmic staining in epithelial cells of both the small and large intestine whereas no staining was seen with Hyb213-1. The number of DMBT1(gp340) positive epithelial cells, stained with Hyb213-6, was significantly up regulated in inflammatory colon tissue sections from patients with ulcerative colitis (p<0.0001) and Crohn's disease (p = 0.006) compared to normal colon tissue. Immunohistochemical analysis of trefoil factor TFF1, 2 and 3 showed that TFF1 and 3 localized to goblet cells in both normal colon tissue and in tissue from patients with ulcerative colitis or Crohn's disease. No staining for TFF2 was seen in goblet cells in normal colon tissue whereas the majority of tissue sections in ulcerative colitis and Crohn's disease showed sparse and scattered TFF2 positive goblet cells. DMBT1 and TFF proteins did therefore not co-localize in the same cells but localized in adjacent cells in the colon. The interaction between DMBT1(gp340) and trefoil TFFs proteins was investigated using an ELISA assay. DMBT1(gp340) bound to solid-phase bound recombinant dimeric TFF3 in a calcium dependent manner (p<0.0001) but did not bind to recombinant forms of monomeric TFF3, TFF2 or glycosylated TFF2. This implies a role for DMBT1 and TFF3 together in inflammatory bowel disease.


Assuntos
Doenças Inflamatórias Intestinais/genética , Peptídeos/genética , Receptores de Superfície Celular/genética , Western Blotting , Proteínas de Ligação ao Cálcio , Proteínas de Ligação a DNA , Dimerização , Eletroforese em Gel de Poliacrilamida , Humanos , Peptídeos/metabolismo , Ligação Proteica , Receptores de Superfície Celular/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Fator Trefoil-2 , Fator Trefoil-3 , Proteínas Supressoras de Tumor , Regulação para Cima
3.
J Pediatr Gastroenterol Nutr ; 51(3): 280-2, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20512060

RESUMO

OBJECTIVE: Eosinophilic oesophagitis (EE) is a clinical entity characterised by a set of symptoms and eosinophilic infiltration of the oesophageal epithelium. Recent reports indicate that EE is increasingly diagnosed in paediatric patients. We aimed to evaluate the epidemiology of paediatric EE in a European population. DESIGN: Infants and children in the Region of Southern Denmark were prospectively referred for further evaluation of symptoms of gastroesophageal reflux disease (GERD) after treatment failure with a proton pump inhibitor. The evaluation included endoscopy, 24-hour oesophageal pH-metry, histology of oesophageal biopsies, and investigations for food allergy (double-blind, placebo-controlled food challenge, skin prick test, S-IgE antibodies, atopy patch test). RESULTS: Of the 78 referred patients, 28 qualified for a diagnosis of GERD. Six children had >15 eosinophils per high-power field in biopsies from the oesophageal mucosa and qualified for the diagnosis of EE. The median age at diagnosis was 9.6 years. In 4 of the 6 patients, food allergy was confirmed by double-blind, placebo-controlled food challenge. In the Region of Southern Denmark with a paediatric population of 256,164 between 0 and 16 years of age, a yearly incidence of EE of 0.16/10,000 was estimated. CONCLUSION: We report a European prospective study of EE. It was documented in 6 of 78 patients with symptoms of GERD corresponding to an annual incidence of 0.16/10,000 infants and children.


Assuntos
Esofagite Eosinofílica/epidemiologia , Esôfago/imunologia , Hipersensibilidade Alimentar/epidemiologia , Refluxo Gastroesofágico/epidemiologia , Adolescente , Fatores Etários , Biópsia , Criança , Pré-Escolar , Dinamarca/epidemiologia , Método Duplo-Cego , Esofagite Eosinofílica/complicações , Eosinófilos , Feminino , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/diagnóstico , Refluxo Gastroesofágico/complicações , Humanos , Lactente , Masculino , Mucosa/imunologia , Prevalência , Estudos Prospectivos
4.
Scand J Gastroenterol ; 45(9): 1029-35, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20504244

RESUMO

OBJECTIVE: Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) in childhood share aspects of symptomatology. In order to characterize EE and GERD in infants and children with symptoms of GERD we performed a prospective investigation including prolonged esophageal pH measurement, multiple intraluminal impedance (MII) and esophageal wall estimation by endoscopic ultrasound (EUS). MATERIAL AND METHODS: Infants and children (0-15 years) with typical symptoms of GERD persisting after a 14-days proton pump inhibitor trial were included in a prospective study protocol. Upper endoscopy and EUS of the esophageal wall were performed followed by combined esophageal MII and pH measurement for 24 h. RESULTS: A total of 78 infants and children were investigated: EE patients (n = 6), GERD patients (n = 28) and a group of infants and children with normal investigations (n = 44). The GERD group did not show a significantly higher number of non-acid reflux episodes (p = 0.9) than the patients with normal investigations. In all patients gastroesophageal reflux regularly extended into the proximal esophagus. EUS in four EE patients suggested an increased thickness of the mucosal layers both in the distal and in the proximal part of the esophagus. CONCLUSIONS: Esophageal MII indicated that neutral non-acid reflux episodes do not occur frequently in pediatric GERD or in EE. MII and pH-metry indicated that the majority of reflux episodes both in patients and controls pass into the proximal esophagus. EUS measurements suggested in EE patients a thickened mucosa both in the proximal and the distal part of the esophagus as compared to children with GERD and disease controls.


Assuntos
Esofagite Eosinofílica/diagnóstico por imagem , Refluxo Gastroesofágico/diagnóstico por imagem , Pré-Escolar , Impedância Elétrica , Endossonografia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Lactente , Masculino
5.
Dis Colon Rectum ; 51(7): 1146-8, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18437493

RESUMO

Adenocarcinomas in relation to the ileal J-pouch after restorative proctocolectomy for ulcerative colitis have been recently reported with increasing frequency. All previously reported cases have occurred in patients with their ileal pouch in situ. We report a case of adenocarcinoma in the anal canal 11 years after removal of a failed ileal J-pouch. Mucosectomy had been performed at the restorative proctocolectomy. The anus had been left in place at the pouch excision because of severe fibrosis in the pelvis. If it is decided to remove an ileal pouch permanently, a total abdominoperineal excision should be performed, particularly in patients with risk factors for cancer development.


Assuntos
Adenocarcinoma Mucinoso/etiologia , Colite Ulcerativa/cirurgia , Bolsas Cólicas/patologia , Neoplasias Retais/etiologia , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/patologia , Anastomose Cirúrgica , Biópsia , Diagnóstico Diferencial , Evolução Fatal , Seguimentos , Humanos , Ileostomia , Masculino , Pessoa de Meia-Idade , Proctocolectomia Restauradora/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Fatores de Tempo , Tomografia Computadorizada por Raios X
7.
Ugeskr Laeger ; 170(1): 25-30, 2008 Jan 07.
Artigo em Dinamarquês | MEDLINE | ID: mdl-18208710

RESUMO

Polyps are reported in 3-5% of adults undergoing upper gastrointestinal endoscopy. The most common types in the stomach are fundic gland polyps, followed by hyperplastic polyps and adenomas. Gastric metaplasia, adenomas and inflammatory polyps are the most common polyps in the duodenum. Treatment options and aggressiveness should be balanced by detailed knowledge of the malignant potential of the different polyps as well as the symptoms, the patient's age and comorbidity.


Assuntos
Duodenopatias/patologia , Pólipos Intestinais/patologia , Pólipos/patologia , Gastropatias/patologia , Adenoma/patologia , Adenoma/terapia , Adulto , Duodenopatias/terapia , Neoplasias Duodenais/patologia , Neoplasias Duodenais/terapia , Duodenoscopia , Gastroscopia , Humanos , Hiperplasia , Pólipos Intestinais/terapia , Pólipos/terapia , Gastropatias/terapia
8.
Ugeskr Laeger ; 169(21): 2029-32, 2007 May 21.
Artigo em Dinamarquês | MEDLINE | ID: mdl-17553386

RESUMO

This screening study was performed to determine the prevalence of coeliac disease (CD) in children with type 1 diabetes (T1D) and to estimate the clinical effects of a gluten-free diet. In the region of Southern Denmark all patients under 16 years of age with T1D were identified and 269 (89%) were included. CD was diagnosed in 33 (12.3%). Patients with CD had a lower height SDS and weight SDS and were younger at diabetes onset. After 2 years on a gluten-free diet there were significant improvements in clinical and biochemical parameters. We recommend screening of CD in all children with T1D.

9.
Acta Oncol ; 46(3): 355-60, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17450471

RESUMO

Case-control studies and short term prospective studies have suggested that selected groups of patients with precursors of colorectal cancer may benefit from colonoscopic surveillance after initial removal of adenomas. The aim of the present study was to demonstrate such a possible benefit from long term (1-24 years) colonoscopic surveillance in a population of patients with all types of adenomas regardless of size and way of removal. Two thousand and forty-one patients with a first time diagnosis of colorectal adenoma were included in prospective surveillance between year 1978 and 2002. All adenomas were considered. Incidence of CRC and mortality from CRC was calculated, using age, sex, and calendar specific number of person years of follow-up for comparison with the standard Danish population. CRC was found in 27 patients, the expected number being 41 (RR 0.65, 95% CI 0.43-0.95). Three of the 27 patients died from CRC, the expected number being 25 (RR 0.12, 95% CI 0.03-0.36). A total of 6 289 colonoscopies resulted in severe complications in 20 patients and two died from complications. Long-term colonoscopic surveillance may reduce incidence of CRC as well as mortality in patients with sporadic adenomas. The benefit is reduced to a minor degree by complications from surveillance.


Assuntos
Adenoma/diagnóstico , Adenoma/epidemiologia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Vigilância da População , Adenoma/mortalidade , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colonoscopia/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Dinamarca/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Cooperação do Paciente , Análise de Sobrevida , Fatores de Tempo
10.
Scand J Gastroenterol ; 42(5): 618-27, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17454883

RESUMO

OBJECTIVE: Cardia, non-cardia and intestinal and diffuse subtypes of gastric cancer may have different trends and etiological factors. However, the available information is not always collected in population cancer registries, and heterogeneous criteria have been applied for the histopathological classification of tumors. We describe the pathological features of incident gastric and esophageal cancers identified within the European Prospective Investigation into Cancer and Nutrition (EPIC). MATERIAL AND METHODS: In an investigation on gastric and esophageal cancer (EUR-GAST) in the EPIC project, a validation study of diagnoses reported by EPIC centers was conducted by a European panel of pathologists. Original pathology reports, stained slides of tumors and the respective paraffin blocks were requested from the centers. RESULTS: The whole series encompassed 467 cancer cases (gastric and esophageal cancers). Material was available for histopathological validation in 263 cases (56%); in the remaining cases, information was retrieved from the original reports (n=110; 24%) or codes provided by the EPIC centers (n=94; 20%). Among cases submitted to histopathological validation reported originally as unknown histotype or unknown site, a specific diagnosis was made in 95% and 74% of the cases, respectively. In cases for which only the original reports were available, the respective percentages were 46% and 67%. Gastric adenocarcinomas were classified according to site (cardia (29.4%), non-cardia (48.2%) and unknown (22.4%)) and histological type (intestinal (33.4%), diffuse (33.7%) and mixed, unclassified or unknown (32.9%)). Frequency of cardia was higher in Northern countries (35%) than in Mediterranean countries (18%). CONCLUSIONS: In addition to providing epidemiological data within the EPIC cohort on gastric and esophageal adenocarcinomas, the results reported here confirm the relevance of a validation study, notably for multicenter studies.


Assuntos
Adenocarcinoma/patologia , Neoplasias Esofágicas/patologia , Inclusão em Parafina/métodos , Neoplasias Gástricas/patologia , Adenocarcinoma/classificação , Adenocarcinoma/epidemiologia , Adulto , Idoso , Diagnóstico Diferencial , Neoplasias Esofágicas/classificação , Neoplasias Esofágicas/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Neoplasias Gástricas/classificação , Neoplasias Gástricas/epidemiologia
11.
Horm Res ; 67(4): 184-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17114887

RESUMO

BACKGROUND: In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation. METHODS: In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. RESULTS: Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease. One patient had a paternal KCNJ11 mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous ABBC8 mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies. CONCLUSION: A rapid analysis of the entire ABBC8 and KCNJ11 genes should not stand alone in the preoperative assessment of patients with CHI, except for the case of maternal, or homozygous/compound heterozygous disease-causing mutations.


Assuntos
Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/genética , Testes Genéticos/métodos , Transportadores de Cassetes de Ligação de ATP/genética , Hiperinsulinismo Congênito/cirurgia , Diagnóstico Diferencial , Genótipo , Humanos , Recém-Nascido , Mutação , Fenótipo , Canais de Potássio/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Cuidados Pré-Operatórios , Receptores de Droga/genética , Receptores de Sulfonilureias
12.
Diabetes Care ; 29(11): 2452-6, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17065683

RESUMO

OBJECTIVE: This study was performed to 1) determine the prevalence of celiac disease in Danish children with type 1 diabetes and 2) estimate the clinical effects of a gluten-free diet (GFD) in patients with diabetes and celiac disease. RESEARCH DESIGN AND METHODS: In a region comprising 24% of the Danish population, all patients <16 years old with type 1 diabetes were identified and 269 (89%) were included in the study. The diagnosis of celiac disease was suspected in patients with endomysium and tissue transglutaminase antibodies in serum and confirmed by intestinal biopsy. Patients with celiac disease were followed for 2 years while consuming a GFD. RESULTS: In 28 of 33 patients with celiac antibodies, an intestinal biopsy showed villous atrophy. In 5 patients, celiac disease had been diagnosed previously, giving an overall prevalence of 12.3% (95% CI 8.6-16.9). Patients with celiac disease had a lower SD score (SDS) for height (P < 0.001) and weight (P = 0.002) than patients without celiac disease and were significantly younger at diabetes onset (P = 0.041). A GFD was obtained in 31 of 33 patients. After 2 years of follow-up, there was an increase in weight SDS (P = 0.006) and in children <14 years old an increase in height SDS (P = 0.036). An increase in hemoglobin (P = 0.002) and serum ferritin (P = 0.020) was found, whereas HbA(1c) remained unchanged (P = 0.311) during follow-up. CONCLUSIONS: This population-based study showed the highest reported prevalence of celiac disease in type 1 diabetes in Europe. Patients with celiac disease showed clinical improvements with a GFD. We recommend screening for celiac disease in all children with type 1 diabetes.


Assuntos
Doença Celíaca/dietoterapia , Doença Celíaca/epidemiologia , Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 1/epidemiologia , Dieta para Diabéticos/métodos , Adolescente , Biópsia , Doença Celíaca/patologia , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Seguimentos , Glutens , Humanos , Masculino , Programas de Rastreamento , Prevalência
14.
Scand J Gastroenterol ; 41(6): 737-43, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16716975

RESUMO

OBJECTIVE: Guidelines for surveillance of patients with previous sporadic colorectal adenomas are based on retrospective long-term follow-up and prospective short-term studies. The aim of the present studies was to compare relative risk (RR) of new neoplasia as well as complications, using different intervals between examinations in long-term surveillance. MATERIAL AND METHODS: Between l98l and l991, patients with pedunculated and small, flat and sessile adenomas were allocated at random to a 24 months (group A) or 48 months (group B) interval between surveillance colonoscopies (n=671). Patients with flat and sessile adenomas greater than 5 mm in diameter were randomized to intervals of 6 months (group C) or 12 months (group D) between l981 and 1987 (n=73). Finally, 200 patients with similar adenomas as in groups C and D were randomized to 12 months (group E) or 24 months (group F) from 1988 to 2000. The study ended in 2002. RESULTS: Advanced adenomas were equally as frequent in group A and group B, but colorectal cancer (CRC) was found significantly more often in group B (RR = 6.2 (1.0-117.4)). Severe complications occurred in 4 patients in group A and 2 patients in group B. Advanced new adenomas tended to be more frequent in group D than in C (p=0.08), but only one CRC was detected and this was in group C. There was no significant difference in the risk of CRC between the E and F groups, but the two cancers in group E were both early stage, in contrast to those in group F. Severe complications were seen in one patient in group E and also in group F. CONCLUSIONS: The results suggest that 2-year intervals should be used between colonoscopies in patients with previous pedunculated adenomas and small, flat and sessile adenomas, whereas larger, flat and sessile adenomas may need intervals of 1 year.


Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Vigilância da População , Adenoma/patologia , Adenoma/cirurgia , Distribuição por Idade , Fatores Etários , Idoso , Colonoscopia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo
15.
J Histochem Cytochem ; 54(10): 1075-86, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16517973

RESUMO

The aim of this study was to evaluate seven anti-TIMP-1 (tissue inhibitor of metalloproteinase-1) monoclonal antibodies by immunohistochemical (IHC) staining of formalin-fixed, paraffin-embedded (FFPE) tissue. Detection of the TIMP-1 protein was studied by IHC in FFPE human archival normal and neoplastic samples. Indirect IHC technique was used, and the seven antibodies (clones VT1, VT2, VT4, VT5, VT6, VT7, and VT8) were tested in various concentrations using different pretreatment protocols. All seven VT antibodies specifically immunostained the cytoplasm of islets of Langerhans cells in normal pancreas, epithelial cells of hyperplastic prostate, tumor cells of medullary thyroid carcinoma, and fibroblast-like cells of malignant melanoma. Specificity of the anti-TIMP-1 antibodies was confirmed by several controls, e.g., Western blotting on proteins extracted from FFPE tissue showed that the VT7 antibody reacted specifically with a protein band of approximately 28 kDa, corresponding to the molecular mass of TIMP-1. However, sensitivity varied with the different antibodies. Use of heat-induced epitope retrieval (HIER) and the VT7 clone applied at low concentrations demonstrated more intense immunoreactivity with the TIMP-1-positive cell types compared to the other six clones. Furthermore, when tested on a range of normal and neoplastic endocrine tissues, the VT7 clone demonstrated immunoreactivity with all neuroendocrine cell types. In conclusion, all seven antibodies detected TIMP-1 protein in various normal and neoplastic FFPE tissues, but one clone, VT7, was superior for IHC staining of TIMP-1 in FFPE tissue sections when using HIER.


Assuntos
Anticorpos Monoclonais , Inibidor Tecidual de Metaloproteinase-1/imunologia , Especificidade de Anticorpos , Fixadores , Formaldeído , Humanos , Imuno-Histoquímica , Neoplasias/metabolismo , Sistemas Neurossecretores/metabolismo , Inclusão em Parafina , Sensibilidade e Especificidade
16.
Carcinogenesis ; 27(7): 1497-501, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16571648

RESUMO

The risk of gastric cancer (GC) associated with dietary intake of nitrosodimethylamine (NDMA) and endogenous formation of nitroso compounds (NOCs) was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC). The study included 521,457 individuals and 314 incident cases of GC that had occurred after 6.6 average years of follow-up. An index of endogenous NOC (ENOC) formation was estimated using data of the iron content from meat intake and faecal apparent total NOC formation according to previous published studies. Antibodies to Helicobacter pylori and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control within the cohort. Exposure to NDMA was < 1 microg on average compared with 93 mug on average from ENOC. There was no association between NDMA intake and GC risk (HR, 1.00; 95% CI, 0.7-1.43). ENOC was significantly associated with non-cardia cancer risk (HR, 1.42; 95% CI, 1.14-1.78 for an increase of 40 microg/day) but not with cardia cancer (HR, 0.96; 95% CI, 0.69-1.33). Although the number of not infected cases is low, our data suggest a possible interaction between ENOC and H.pylori infection (P for interaction = 0.09). Moreover, we observed an interaction between plasma vitamin C and ENOC (P < 0.02). ENOC formation may account for our previously reported association between red and processed meat consumption and gastric cancer risk.


Assuntos
Adenocarcinoma/epidemiologia , Dieta , Nitrosaminas/metabolismo , Nitrosaminas/farmacologia , Neoplasias Gástricas/epidemiologia , Adenocarcinoma/etiologia , Animais , Ácido Ascórbico/sangue , Estudos de Casos e Controles , Bovinos , Dimetilnitrosamina/metabolismo , Europa (Continente) , Feminino , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Humanos , Ferro , Masculino , Carne/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/etiologia
17.
Appl Immunohistochem Mol Morphol ; 14(1): 115-21, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16540742

RESUMO

Testing for microsatellite instability (MSI) has become an important step in the planning of therapeutic and follow-up procedures for patients with colorectal cancer, both as a prognostic marker and as a screening tool for hereditary non-polyposis colorectal cancer. Today the gold standard for MSI testing is based on the polymerase chain reaction. Immunohistochemistry may represent an alternative or complement to molecular MSI testing. Antibodies against the protein products of the most commonly affected mismatch repair genes (hMLH1, hMSH2, hMSH6, and hPMS2) have been available for some time now. However, the quality of the primary antibody and optimization of the antigen retrieval methods are essential to get reproducible results. The aim of the present study was to test and optimize a panel of antibodies against the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 using biotin-free, polymer-based visualization systems. The antibodies were tested on multitissue blocks containing normal tissue and tumor tissue from patients with known microsatellite-stable and microsatellite-instable tumors. For all four antibody groups, the chosen clones gave specific and reproducible staining. Furthermore, with the PowerVision+ detection system, the influence of endogenous biotin was eliminated, the incubation time with the primary antibody was significantly reduced, and the primary antibody could be further diluted. The authors found that immunohistochemistry may provide a cost-effective and time-saving complement to the molecular MSI analysis, and using the PowerVision+ detection system has greatly decreased the turnaround time as well as reduced the cost of immunohistochemistry in the authors' laboratory.


Assuntos
Adenosina Trifosfatases/análise , Anticorpos/química , Proteínas de Transporte/análise , Neoplasias Colorretais/patologia , Enzimas Reparadoras do DNA/análise , Proteínas de Ligação a DNA/análise , Imuno-Histoquímica/métodos , Proteína 2 Homóloga a MutS/análise , Proteínas Nucleares/análise , Proteínas Adaptadoras de Transdução de Sinal , Adenosina Trifosfatases/imunologia , Anticorpos/classificação , Anticorpos/metabolismo , Biotina , Proteínas de Transporte/imunologia , Neoplasias Colorretais/química , Neoplasias Colorretais/diagnóstico , Enzimas Reparadoras do DNA/imunologia , Proteínas de Ligação a DNA/imunologia , Humanos , Endonuclease PMS2 de Reparo de Erro de Pareamento , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/imunologia , Proteínas Nucleares/imunologia
18.
Ugeskr Laeger ; 167(44): 4170-2, 2005 Oct 31.
Artigo em Dinamarquês | MEDLINE | ID: mdl-16266570

RESUMO

Pathological assessment of colorectal cancer resection specimens is the most significant prognostic indicator. This includes determination of TNM stage, tumour type and grade, status of resection margins, extramural vascular and perineural invasion, and molecular features such as defects in the mismatch repair system. The pathological assessment contributes significantly to the quality control of surgery and preoperative staging. Reporting should be standardized by using DSPAC's registration scheme for colorectal carcinomas.


Assuntos
Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos do Sistema Digestório/normas , Manejo de Espécimes/normas , Bancos de Espécimes Biológicos/normas , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/normas , Humanos , Técnicas de Diagnóstico Molecular , Estadiamento de Neoplasias/normas , Guias de Prática Clínica como Assunto , Prognóstico , Garantia da Qualidade dos Cuidados de Saúde , Controle de Qualidade
19.
Carcinogenesis ; 26(6): 1129-37, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15760920

RESUMO

Abnormalities in the expression of DMBT1 (deleted in malignant brain tumors 1) have been implicated in the development of esophageal, gastric and colorectal cancers of the alimentary tract, but the underlying mechanism remains unclear. In the present study, using the gastric cell line AGS, we identified two intracellular signaling molecules protein kinase C (PKC) and extracellular signal-related kinase (ERK). They mediated both the phorbol myristate acetate (PMA) downregulation of DMBT1 expression and the initiation of cell differentiation, which was measured by cell cycle withdrawal and the induction of the tissue-specific marker trefoil factor 1 (TFF1). A time-course study showed that following the PMA activation of ERK kinase, the induction of TFF1 and the reduction of DMBT1 were detected at the same time point. We then demonstrated a minimal level of DMBT1 in proliferating AGS cells seeded at low density, where ERK activity was high. Reduction of ERK activity, either by an ERK inhibitor PD98059 or by high-density seeding, significantly reduced AGS cell growth judged by CFSE labeling. This cellular effect was elicited by cyclin D/p21 (Cip/Waf1) and G(0)/G(1) arrest, and was accompanied by a marked increase in DMBT1-expressing cells. Finally, we showed that siRNA directed against DMBT1 had no effect on the induction of a cell growth arrest marker, gut-enriched Kruppel-like factor (GKLF), but reduced the PMA induction of TFF1. Along with its upregulation coinciding with G(0)/G(1) arrest, and its attenuation in differentiated cells, these results suggest that the transient induction of DMBT1 is apparently specific at an early stage of gastric epithelial differentiation-like process, when it may play a role in cell fate decision. Consistent with such a potential function, we detected frequent abnormalities of the DMBT1 expression in the specimens of human gastric adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Aglutininas/biossíntese , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Mucosa Gástrica/metabolismo , Receptores de Superfície Celular/biossíntese , Neoplasias Gástricas/metabolismo , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Proteínas de Ligação ao Cálcio , Proteínas de Ciclo Celular/biossíntese , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D3 , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/biossíntese , Proteínas de Ligação a DNA/metabolismo , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Flavonoides/farmacologia , Mucosa Gástrica/enzimologia , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like , Especificidade de Órgãos , Proteína Quinase C/metabolismo , Proteínas/metabolismo , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Transcrição/metabolismo , Fator Trefoil-1 , Proteínas Supressoras de Tumor
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