RESUMEN
Different rehabilitation models for persons diagnosed with disorders of consciousness have been proposed in Europe during the last decade. In Italy, the Ministry of Health has defined a national healthcare model, although, to date, there is a lack of information on how this has been implemented at regional level. The INCARICO project collected information on different regional regulations, analysing ethical aspects and mapping care facilities (numbers of beds and medical units) in eleven regional territories. The researchers found a total of 106 laws; differences emerged both between regions and versus the national model, showing that patients with the same diagnosis may follow different pathways of care. An ongoing cultural shift from a treatment-oriented medical approach towards a care-oriented integrated biopsychosocial approach was found in all the welfare and healthcare systems analysed. Future studies are needed to explore the relationship between healthcare systems and the quality of services provided.
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Necesidades y Demandas de Servicios de Salud , Estado Vegetativo Persistente/rehabilitación , Política de Salud , Capacidad de Camas en Hospitales , Humanos , Italia , Programas Nacionales de Salud , RegionalizaciónRESUMEN
Hepatitis C virus (HCV) chronic infection can be associated with extrahepatic manifestations such as mixed cryoglobulinaemia and lymphoproliferative disorders that are endowed with increased rates of morbidity and all-cause mortality. In this study, we used flow cytometry to evaluate the effect of interferon-free antiviral treatment on peripheral blood lymphocytes in HCV-infected patients with or without associated lymphoproliferative disorders. Flow cytometry analysis of peripheral blood lymphocytes was performed at baseline and at the end of treatment. In HCV-infected patients with lymphoproliferative disorders, we evaluated immunoglobulin (Ig) light chain κ/λ ratio variations as a measure of monoclonal B-cell response to antiviral therapy. Healthy volunteers were enrolled as controls. A total of 29 patients were included, nine with and 20 without lymphoproliferative disorders. Sustained virological response was achieved in 29 of 29 patients. We observed a significant reduction in the B-cell compartment (39% global reduction) in eight of nine HCV-infected patients with lymphoproliferative disorders after viral clearance. We recognized the same trend, even if less pronounced, in HCV-infected patients without lymphoproliferative disorders (9% global reduction). Among HCV-infected patients with lymphoproliferative disorders, three showed an improvement/normalization of the immunoglobulin light chain ratio, whereas in the remaining six patients monoclonal B cells persisted to be clonally restricted even 1 year after the end of treatment. Our data show that DAAs treatment can be effective in reducing the frequency of pathological B cells in the peripheral blood of HCV-infected patients affected by HCV-associated lymphoproliferative disorders; however, monoclonal populations can persist after viral eradication.
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Antivirales/uso terapéutico , Linfocitos B/inmunología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/patología , Inmunidad Celular , Adulto , Anciano , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Respuesta Virológica SostenidaRESUMEN
Vectors combining the heat shock proteins (HSPs) promoter with the catalytic subunit A of the diphtheria toxin (DTA) or its variants, cross-reacting material (CRM) 176 and 197, were engineered to investigate the effect of bacterial toxins on pancreatic cancer (PC) cells. Three heat-inducible enhanced green fluorescent protein (eGFP)-expression vectors were obtained: V1 (91% homology to HSPA6), V2 (five heat shock elements upstream the minimal HSPA6 promoter) and V3 (V1 and V2 combined). The highest eGFP transcription and translation levels were found in V3 transfected PC cells. The V3 promoter was used to control DTA, CRM176 and CRM197 expression, treatment response being investigated in four PC cell lines. DTAwt or CRM176 transfected cell growth was completely arrested after heat shock. CRM197 toxin presumed to be inactive, caused mild distress at 37 degrees C and induced a 25-50% reduction in cell growth after heat shock. Preliminary in vivo findings showed that heat treatment arrests tumor growth in DTA197 stably transfected PSN1 cells. In conclusion, the efficient HSP promoter identified in this study may be extremely useful in controlling the transcription of toxins such as CRM197, which have lethal dose-related effects, and may thus be a promising tool in PC gene therapy in vivo.
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Proteínas Bacterianas/genética , Toxina Diftérica/genética , Terapia Genética/métodos , Proteínas HSP70 de Choque Térmico/genética , Neoplasias Pancreáticas/terapia , Fragmentos de Péptidos/genética , Animales , Proteínas Bacterianas/biosíntesis , Línea Celular Tumoral , Toxina Diftérica/biosíntesis , Femenino , Vectores Genéticos , Proteínas de Choque Térmico/biosíntesis , Proteínas de Choque Térmico/genética , Respuesta al Choque Térmico/genética , Humanos , Ratones , Ratones Desnudos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fragmentos de Péptidos/biosíntesis , Regiones Promotoras Genéticas , TransfecciónRESUMEN
The present report focuses on the diagnosis of celiac disease and its pathogenesis, which depends on a genetic predisposition (HLA DQ2 or DQ8 haplotypes), gluten ingestion and T cell activation, type II transglutaminase (TG2), the autoantigen recognized by the antiendomysial antibody playing a key role. IgA class antibody anti-environmental (gliadin) and endogenous (TG2) antigens are present in the sera of patients with celiac disease. The anti-TG2 antibody has the best available diagnostic accuracy, especially when measured employing second generation ELISA tests, which use the human TG2 antigen, or immunochemiluminescent assay, which is highly sensitive. A diagnosis of celiac disease must always be confirmed by the histological evaluation of multiple duodenal mucosa specimens, and serology is recommended for follow-up controls.
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Enfermedad Celíaca/diagnóstico , Técnicas de Laboratorio Clínico , Anticuerpos/análisis , Anticuerpos/inmunología , Enfermedad Celíaca/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Gliadina/inmunología , Humanos , Sensibilidad y Especificidad , Transglutaminasas/inmunologíaRESUMEN
This review describes: 1. The main genetic alterations found in pancreatic cancer (EGF-R overexpression, SST-2 somatostatin receptor loss of expression, k-ras, p53 mutations and DPC4 mutations) and the effect of their replacements by gene therapy on tumor growth; 2. The use of suicide genes (HSV-TK and CD) for pancreatic cancer gene therapy in vitro and in vivo; 3. The implications for pancreatic cancer treatment when using cytotoxic bacterial toxins; 4. Viral and non-viral delivery systems for the transfer of therapeutical genes into pancreatic cancer cells. Overall both the correction of pancreatic cancer cells main genetic alterations and the use of suicide genes allow only partial tumor regression in vitro and in vivo. The lack of a 100% effect for any studied strategy considered alone, indicates the need for combined therapies to achieve a satisfactory treatment of this tumor.
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Genes Transgénicos Suicidas/genética , Terapia Genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Animales , Toxinas Bacterianas/farmacología , Citocinas/farmacología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pancreáticas/patologíaAsunto(s)
Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Interleucina-12/genética , Polimorfismo de Nucleótido Simple , Subunidades de Proteína/genética , Neoplasias Gástricas/genética , Adenocarcinoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad , Humanos , Subunidad p35 de la Interleucina-12 , Subunidad p40 de la Interleucina-12 , Masculino , Persona de Mediana Edad , Repeticiones de MinisatéliteRESUMEN
BACKGROUND: We investigated in vitro whether IL-1beta and TGF-beta1 affect pancreatic cancer cell growth, adhesion to the extracellular matrix and Matrigel invasion. MATERIALS AND METHODS: Adhesion to fibronectin, laminin and type I collagen, and Matrigel invasion after stimulation with saline, IL-1beta and TGF-beta1 were evaluated using three primary and three metastatic pancreatic cancer cell lines. RESULTS: Extracellular matrix adhesion of control cells varied independently of the metastatic characteristics of the studied cell lines, whereas Matrigel invasion of control cells was partly correlated with the in vivo metastatic potential. IL-1beta did not influence extracellular matrix adhesion, whereas it significantly enhanced the invasiveness of three of the six cell lines. TGF-beta1 affected the adhesion of one cell line, and exerted contrasting effects on Matrigel invasion of different cell lines. CONCLUSIONS: IL-1beta enhances the invasive capacity of pancreatic cancer cells, whereas TGF-beta1 has paradoxical effects on pancreatic cancer cells; this makes it difficult to interfere with TGF-beta1 signaling in pancreatic cancer treatment.
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Interleucina-1/farmacología , Invasividad Neoplásica/patología , Neoplasias Pancreáticas/patología , Factor de Crecimiento Transformador beta/farmacología , Adhesión Celular , Línea Celular Tumoral , Matriz Extracelular/metabolismo , Humanos , Neoplasias Pancreáticas/metabolismo , Factor de Crecimiento Transformador beta1RESUMEN
BACKGROUND AND AIMS: We verified whether conditioned media (CM) from pancreatic cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3) alter glucose metabolism and gene expression profiles (microarray experiment with a platform of 5000 skeletal muscle cDNA) in mice myoblasts. METHODS: Myoblasts were incubated with control or pancreatic cancer CM for 24 and 48 hours. RESULTS: Lactate significantly increased in CM compared with non-conditioned myoblasts. No variations in expression levels of the main genes involved in glycolysis were found in CM myoblasts. Propionyl coenzyme A carboxylase and isocitrate dehydrogenase 3 beta genes, which encode enzymes of the tricarboxylic acid cycle, were overexpressed, while IGFIIR and VAMP5 genes were underexpressed in CM myoblasts. PAFAH1B1 and BCL-2 genes (intracellular signal transduction) and the serine protease cathepsin G (proteolysis), were overexpressed in CM myoblasts. Tyrosine accumulation in CM myoblasts suggested that proteolysis overcomes protein synthesis. Sorcin, actin alpha, troponin T1, and filamin A were underexpressed in CM myoblasts. CONCLUSIONS: Our findings demonstrate that pancreatic cancer cell conditioned media enhanced lactate production and induced proteolysis, possibly by altering expression levels of a large number of genes, not only those involved in protein biosynthesis and degradation or glucose metabolism, but also those involved in the tricarboxylic acid cycle and in vesicle traffic.
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Glucosa/metabolismo , Neoplasias Pancreáticas/metabolismo , Anciano , Análisis de Varianza , Animales , Línea Celular Tumoral , Medios de Cultivo Condicionados , Femenino , Expresión Génica , Perfilación de la Expresión Génica/métodos , Genes Relacionados con las Neoplasias/genética , Glucólisis , Humanos , Ácido Láctico/análisis , Masculino , Ratones , Persona de Mediana Edad , Mioblastos/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Neoplasias Pancreáticas/enzimología , Neoplasias Pancreáticas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodosRESUMEN
AIM: To study in vivo whether pancreatic cancer tumour growth and metastasis can be modified by a gene construct with HSV-TK suicide gene and IL2 co-expression. METHODS: Seventy-eight female SCID mice were i.p. inoculated with retrovirally transduced or control MIA PaCa 2, CAPAN-1 and PANC-1 cell lines. The animals were then randomly selected for saline or ganciclovir (GCV) treatment from the second week, for a total of two weeks. RESULTS: Most inoculated mice developed tumour nodules and spleen metastases. The liver was colonized by control CAPAN-1 and MIA PaCa 2, but not by PANC-1. Tumours in transduced MIA PaCa 2 cell injected mice were smaller, and in transduced CAPAN-1 injected mice larger, than in control-inoculated mice. There were increased pancreatic and decreased spleen metastases from transduced CAPAN-1, and diminished liver involvement from transduced MIA PaCa 2. No differences were found between mice inoculated with transduced and control PANC-1 cell lines. GCV treatment had no effect on tumour's size or metastases. CONCLUSIONS: The HSV-TK suicide gene does not confer GCV sensitivity to pancreatic cancer in this in vivo model. Different pancreatic cancer cell lines cause different growth and metastasis patterns after inoculation in SCID mice, possibly because of variations in their inherent characteristics. The different effects of our vector on cell growth and metastasis may be attributable to the effects of the immunostimulatory cytokine IL2.
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Terapia Genética , Neoplasias Pancreáticas/terapia , Timidina Quinasa/genética , Animales , Antivirales/uso terapéutico , Femenino , Ganciclovir/uso terapéutico , Inyecciones Intraperitoneales , Ratones , Ratones SCID , Neoplasias Pancreáticas/patología , Distribución Aleatoria , Retroviridae/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Simplexvirus/enzimología , Neoplasias del Bazo/secundario , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
AIMS: The aims of this study were 1) to investigate the mRNA pattern of CD44 variants in three primary (MIA PaCa 2, PANC-1, PSN-1) and two metastatic (CAPAN-1, SUIT-2) pancreatic cancer (PC) cell lines; 2) to ascertain whether the genetic transfer of CD44s and CD44v10 modifies the adhesion of PC cells to the extracellular matrix (ECM) in vitro and their metastatic behavior in vivo. METHODS: CD44 mRNA analysis was done by means of RT-PCR. Adhesion to ECM the was assessed using coated microtiter plates. For the study of CD44v10 insertion in the CAPAN-1 line, liposome-mediated DNA transfer was used. SCID mice were employed for in vivo experiments. RESULTS: CD44v10 mRNA was not expressed by the CAPAN-1 nor by four of the six SUIT-2-derived clones. The stable expression of CD44v10 by modified CAPAN-1 significantly enhanced fibronectin adhesion. Mice without either liver or pancreatic metastases were more frequently found among the animals injected with modified (CD44v10 expressing) than with non-modified CAPAN-1. CONCLUSIONS: 1) It is possible to differentiate between metastatic and non-metastatic PC cells on the basis of CD44v10 expression; 2) CD44v10 seems to be involved in mediating fibronectin adhesion in vitro and in counteracting metastases in vivo.
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Receptores de Hialuranos/fisiología , Metástasis de la Neoplasia/prevención & control , Neoplasias Pancreáticas/patología , Animales , Adhesión Celular , Femenino , Fibronectinas/fisiología , Humanos , Receptores de Hialuranos/genética , Ratones , Ratones SCID , Invasividad Neoplásica , Neoplasias Pancreáticas/química , ARN Mensajero/análisis , Células Tumorales CultivadasRESUMEN
Helicobacter pylori infection outcome might depend on genotypic polymorphisms of both the bacterium and the host. We ascertained: (1) the functionality of H. pylori oipA gene; (2) the polymorphism of the hostinterleukin (IL-1beta) gene (-31 C/T) and of the IL-1RN gene (intron 2 VNTR); (3) the association between the above genes and the histological and pathological outcome of H. pylori infection. One hundred and sixty-five H. pylori positive and 137 H. pylori negative subjects (23 gastric adenocarcinoma, 58 peptic ulcer, 221 gastritis) were studied. oipA was sequenced, IL-1beta was RFLP analysed. Antral and body mucosal biopsies were histologically evaluated. Functional oipA genes were correlated with cagA gene; both genes were significantly associated with gastritis activity, peptic ulcer and gastric adenocarcinoma. In these patients heterozygousIL-1RN 1/2 and IL-1beta C/T genotypes were more frequent than in gastritis patients. Intestinal metaplasia was associated with cagA, functional oipA and IL-1RN 2 allele. In conclusion, peptic ulcer and the preneoplastic intestinal metaplasia are associated with H. pylori virulence genes and with IL-1RN 2 host allele. An interplay between bacterial virulence factors and cytokines genotypes, is probably the main route causing H. pylori infection to lead to benign mild disease, benign severe disease or preneoplastic lesions.
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Antígenos Bacterianos , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Interleucina-1/genética , Metaplasia/genética , Metaplasia/microbiología , Úlcera Péptica/microbiología , Sialoglicoproteínas/genética , Adenocarcinoma/genética , Adenocarcinoma/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Proteínas Bacterianas/genética , Endoscopía , Femenino , Mucosa Gástrica/patología , Genotipo , Heterocigoto , Humanos , Proteína Antagonista del Receptor de Interleucina 1 , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologíaRESUMEN
OBJECTIVE: It has been suggested that the molecular identification of cancer cells in the circulation may be useful in predicting the presence of micrometastasis in several cancer types. The aim of the present study was therefore to assess the feasibility of CEA mRNA identification in blood for diagnosing and staging colorectal, gastric and pancreatic cancer. METHODS: We studied 16 control subjects, 69 patients with colorectal (CRC), 30 with gastric (GC), 27 with pancreatic cancer (PC) and 8 with benign diseases of the pancreatobiliary tree. At diagnosis CEA mRNA was identified in peripheral blood by means of a RT-PCR procedure. RESULTS: The specificity of this test in control subjects was 94%, and its sensitivity in identifying CRC, GC and PC were 34, 37 and 41%, respectively. False-positive findings were recorded in 25% patients with benign diseases. No association was found between CEA mRNA and stage in patients with GC or PC. In CRC patients, positive CEA mRNA findings were correlated with local spread (chi(2) = 14.6, p<0.01), lymph node (chi(2) = 18.95, p<0.001) and distant metastasis (chi(2) = 11.3, p<0.001). In these cases, CEA mRNA, but not CEA, was entered in stepwise discriminant analysis to classify the presence of lymph node metastasis. CONCLUSIONS: The molecular detection of micrometastasis in the blood by means of CEA mRNA identification is feasible for colorectal, but not for gastric or pancreatic cancer staging. Further studies are needed in order to define the clinical utility of this marker also in follow-up protocols.
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Biomarcadores de Tumor/sangre , Antígeno Carcinoembrionario/genética , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , ARN Mensajero/sangre , ARN Neoplásico/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , ARN , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patologíaRESUMEN
Our aim was to assess the clinical reliability of mutated K-ras detection in serum or bile for the diagnosis of pancreatic cancer using ME-PCR. DNA was extracted from 1 ml serum obtained from 29 patients with pancreatic cancer and 12 control subjects. ME-PCR was optimized using a mixture of normal DNA added with different amounts of mutated DNA. The analysis of sera obtained from the 29 patients and of bile obtained from 11 pancreatic cancer patients demonstrated the presence of mutated K-ras in two (6.9%) and four cases (36%). By contrast K-ras was not amplifiable in any of the 12 serum samples obtained from healthy controls. In conclusion the DNA obtained from pancreatic cancer patients' sera is suitable for K-ras amplification and for the identification of codon 12 point mutations. However ME-PCR alone has an unsatisfactory sensitivity for the detection of pancreatic cancer using serum DNA as starting template.
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Bilis/química , ADN/análisis , Genes ras , Mutación , Neoplasias Pancreáticas/genética , Reacción en Cadena de la Polimerasa/métodos , Adulto , Anciano , Anciano de 80 o más Años , Codón , ADN/sangre , Análisis Mutacional de ADN/métodos , Electroforesis en Gel de Agar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación Puntual , Células Tumorales CultivadasRESUMEN
OBJECTIVES: To ascertain when the serum determination of the free prostate-specific antigen (PSA)/total PSA (fPSA/tPSA) ratio is clinically useful, and whether the identification of PSA or prostate-specific membrane antigen (PSM) mRNA in circulating cells has diagnostic advantages over the determination of their protein product. METHODS: fPSA, tPSA, and the fPSA/tPSA ratio were determined in the sera of 50 men with benign nonprostatic urologic diseases (EPD), 112 patients with prostate cancer (PCa), and 218 with benign prostatic hyperplasia (BPH). mRNA was extracted from the circulating mononuclear cells of 13 EPD samples, 25 PCa samples, and 38 BPH samples. PSA and PSM mRNA signals were identified in these samples by means of reverse transcriptase-polymerase chain reaction. RESULTS: Overall, at a fixed specificity of 95%, the sensitivity of tPSA was 19% and that of the fPSA/tPSA ratio was 40% in distinguishing PCa from BPH. The fPSA/tPSA ratio allowed the discrimination of PCa from BPH with satisfactory sensitivity and specificity when considering patients less than 60 years of age (100% and 95%, respectively). PSA and PSM mRNA were positive in 1 and 7 of 13 EPD samples, 6 and 13 of 25 PCa samples, and 6 and 17 of 38 BPH samples. The Gleason score did not correlate with tPSA, the fPSA/tPSA ratio, PSA mRNA, or PSM mRNA. CONCLUSIONS: The serum determination of the fPSA/tPSA ratio is an excellent index of PCa for subjects younger than 60 years of age; the clinical utility of PSA mRNA identification in circulating cells needs to be validated by large follow-up studies, and the analysis of PSM mRNA seems to be of no clinical interest.
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Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/genética , Hiperplasia Prostática/sangre , ARN Mensajero/sangre , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The aims of our study were twofold. First, we sought to evaluate in symptomatic children the influence of the Helicobacter pylori genotype on gastritis, abdominal pain, and circulating anti-H. pylori IgG antibodies (anti-H. pylori IgG) or pepsinogen A (PGA) and C (PGC). Additionally, we sought to assess anti-H. pylori IgG, PGA, and PGC patterns in a large cohort (N = 921) of asymptomatic children. MATERIALS AND METHODS: In 183 symptomatic children, H. pylori infection and the presence of gastritis were evaluated by histology. In a subgroup of 20 H. pylori-positive children, the H. pylori genotype was evaluated also by polymerase chain reaction. Nine hundred and twenty-one asymptomatic children, aged 11 to 14 years, were studied by anti-H. pylori IgG, PGA, and PGC serum determination. RESULTS: The infection was found in 33 of 183 symptomatic children; among the 20 H. pylori-positive children for which the H. pylori genotype was available, cagA was present or absent in equal percentages. H. pylori infection was associated with more severe gastritis and higher serum levels of anti-H. pylori IgG and PGC but not with abdominal pain. In infected children, higher levels of anti-H. pylori IgG and the presence of abdominal pain were associated with infections caused by cagA-positive strains. In the cohort of 921 asymptomatic children, raised levels of anti-H. pylori IgG, PGA, and PGC were found in approximately 5% of the cases. CONCLUSIONS: Infection with cagA-positive H. pylori strains can be associated with increased frequency of reported abdominal pain and higher circulating levels of anti-H. pylori IgG. The serological assessment of H. pylori IgG using H. pylori antigens containing significant amounts of cagA protein may, therefore, underestimate the true prevalence of infection.
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Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos , Proteínas Bacterianas/genética , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/genética , Dolor Abdominal , Adolescente , Niño , Preescolar , Endoscopía Gastrointestinal , Femenino , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/inmunología , Helicobacter pylori/aislamiento & purificación , Humanos , Técnicas para Inmunoenzimas/métodos , Lactante , Masculino , Pepsinógeno A/sangre , Pepsinógeno C/sangre , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y EspecificidadRESUMEN
The serum determination of pepsinogen A (PGA) and pepsinogen C (PGC) might indicate gastric mucosal inflammation and atrophy. Body gastric mucosa produces both PGA and PGC, while antral mucosa produces only PGC. Therefore, diseases involving mainly the antrum, such as H. pylori infection, are mainly indicated by the variations in serum PGC than in serum PGA. In agreement, when the antral mucosa is infected by the more virulent cagA positive H. pylori strains, which cause severe inflammation, serum PGC significantly increases. Another indirect indicator of gastric inflammation is polymorphonuclear (PMN) oxidative burst after the stimulation with water extracts from H. pylori culture: this parameter is significantly increased in infected if compared to non-infected subjects. The higher oxidative burst response of peripheral PMN in infected patients, possibly consequent to the release of specific cytokines able to prime PMN towards H. pylori products, is unable to eliminate the infection, but it might concur in damaging the gastric mucosa.
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Estómago/fisiopatología , Biomarcadores/sangre , Mucosa Gástrica/metabolismo , Gastritis/sangre , Infecciones por Helicobacter/sangre , Helicobacter pylori , Humanos , Pepsinógeno A/sangre , Pepsinógeno C/sangreRESUMEN
UNLABELLED: Interleukin 6 (IL-6), an autocrine growth factor for many tumors, seems to favour tumor spread to the liver. Our aims were first to evaluate the pattern of portal and systemic IL-6 levels in patients with pancreatic cancer (PC, n = 18) and chronic pancreatitis (CP, n = 22) compared with controls (CS, n = 20); and second, to ascertain whether there was any relation between IL-6 levels and tumor spread or PC-associated Diabetes mellitus. For all subjects, a fasting serum sample was obtained from a cubital vein; a portal serum sample was obtained from nine PC and three CP patients. In cubital and portal sera we measured IL-6, interleukin 1 beta (IL-1b), CA 19-9, c-reactive protein (CRP) and amylase. Systemic IL-6 levels were significantly higher in PC patients than in CS. In PC, portal IL-6 levels were significantly higher than the corresponding systemic values. The same pattern was found in the three CP patients, whereas IL-1b, CA 19-9, CRP and amylase portal levels were the same as systemic values. No correlation was found between PC stage and systemic or portal IL-6 levels. Portal IL-6 levels were correlated with the corresponding fasting serum glucose values. A significant correlation was found between IL-6 values and CRP, ALT, total bilirubin, GGT and creatinine, but not amylase. IN CONCLUSION: (1) Portal IL-6, which is partly of pancreatic origin, is first metabolised in the liver; (2) Systemic IL-6 reflects hepatic and renal functions rather than local conditions in the pancreas; (3) IL-6 does not appear to influence PC spread; (4) IL-6, which is released in large amounts by the inflamed pancreas, may contribute to determining diabetes, thus interfering with the signal transducing pathways involved in glucose metabolism in liver cells.
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Glucosa/metabolismo , Interleucina-6/sangre , Neoplasias Pancreáticas/sangre , Anciano , Anciano de 80 o más Años , Circulación Sanguínea , Enfermedad Crónica , Diabetes Mellitus/sangre , Femenino , Humanos , Hígado/irrigación sanguínea , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Pancreáticas/patología , Pancreatitis/sangre , Sistema PortaRESUMEN
UNLABELLED: It has been suggested that transforming growth factor beta (TGFb) mediates liver fibrosis, which can be monitored by the serum determination of the N-terminal peptide of type III procollagen (PIIIP) and laminin. Fibrosis is also an important phenomenon in patients with chronic pancreatitis (CP). In 23 patients with CP, 38 with liver cirrhosis (LC) and 20 healthy controls we compared the serum patterns of PIIIP, laminin and TGFb and assessed whether in CP these markers are correlated with exocrine and endocrine function. In patients with LC, PIIIP and laminin levels were significantly higher, whereas TGFb levels were significantly lower than those of controls. In CP patients, no significant variations were found for PIIIP and laminin, although levels were high in 7/23 and in 5/23 patients, respectively. TGFb levels in CP patients were higher than those in LC patients, levels being raised in 6/23 patients. In LC patients an inverse correlation was found between PIIIP and TGFb, whereas in CP patients, a direct correlation was found between TGFb and PIIIP. Moreover, in CP patients, there was also a positive correlation between TGFb and fasting serum glucose levels, while laminin was correlated with PABA test results. IN CONCLUSION: serum biochemical markers of liver fibrosis can be considered of limited value in assessing pancreatic fibrosis; in liver cirrhosis there may be a negative feed-back regulation between TGFb production and the fibrogenetic process; and in chronic pancreatitis TGFb appears to favor fibrosis on the one hand and the development of hyperglycemia on the other.
Asunto(s)
Hiperglucemia/metabolismo , Cirrosis Hepática/metabolismo , Pancreatitis/complicaciones , Pancreatitis/metabolismo , Factor de Crecimiento Transformador beta/sangre , Adulto , Anciano , Bilirrubina/sangre , Biomarcadores , Glucemia/metabolismo , Enfermedad Crónica , Femenino , Fibrosis , Estudios de Seguimiento , Humanos , Laminina/sangre , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Pancreatitis/patología , Procolágeno/metabolismoRESUMEN
BACKGROUND: The neural adhesion molecule N-CAM, a membrane bound glycoprotein, seems to play an important role in the development of normal tissue architecture and in contact-dependent inhibition of cell growth. MATERIALS AND METHODS: We evaluated the behaviour of circulating N-CAM in patients with pancreatic cancer (24 cases) and chronic pancreatitis (15 cases) and compared it with that of 20 controls, 6 patients with colon adenoma, 31 with colorectal cancer or 21 with gastric cancer and ascertained the influence of tumor stage and grade on the findings. RESULTS: N-CAM levels were significantly lower in patients with pancreatic cancer and chronic pancreatitis than in the other groups studied. High levels were found only in few colorectal carcinoma patients (4/31). No correlation was found between tumor stage and N-CAM levels when pancreatic and colorectal cancer were considered. However, low N-CAM levels were found in 50% of advanced, but not in early gastric cancer. When pancreatic, colorectal and gastric cancer were considered, poorly differentiated (G3) had lower levels of N-CAM than well (G1) or moderately (G2) differentiated tumors. The variations found in circulating N-CAM were comparable to those in CEA but not to those in CA 19-9. CONCLUSIONS: a) perhaps because of its higher aggressiveness, pancreatic cancer is associated with low serum N-CAM levels unlike other gastrointestinal neoplasias; b) the association between aggressiveness and reduced N-CAM levels is borne out by the correlation found with the grade of differentiation; c) the reduced levels found in chronic pancreatitis suggest that this molecule plays a role in stromaparenchymal interactions, which might be altered in the presence of fibrotic phenomena.
Asunto(s)
Neoplasias Gastrointestinales/sangre , Moléculas de Adhesión de Célula Nerviosa/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias Gastrointestinales/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
The present review focuses on the utility of serum tumor markers in screening, diagnosis, prognosis and monitoring of pancreatic cancer. Serum determination of all tumor markers studied offers no help in screening or early diagnosis of pancreatic cancer. For diagnosis, blood group-related antigens, in particular CA 19-9, are considered the best indicators of this neoplasm. However, as occurs with other glycoproteic tumor markers, the circulating levels of CA 19-9 are significantly influenced by jaundice, probably because its liver metabolism is reduced. Therefore, the finding of elevated CA 19-9 levels in jaundiced patients has to be evaluated with caution. Since pancreatic cancer recurrences are not susceptible to treatment, the clinical role of widespread use of tumor marker determination in follow-up programs is limited and calls for a critical evaluation.