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2.
Hepatogastroenterology ; 61(133): 1241-5, 2014.
Article in English | MEDLINE | ID: mdl-25436290

ABSTRACT

Barrett's esophagus is an acquired clinical condition in which the squamous epithelium of the distal esophagus is replaced by a columnar epithelium. The diagnosis requires histological confirmation of specialized intestinal metaplasia, in which goblet cells must be present. Barrett's esophagus is a risk factor for the development of esophageal adenocarcinoma, a tumor with an incidence and mortality have increased alarmingly in recent years in the western world. It has been estimated that the annual incidence of cancer in patients with Barrett's esophagus has increased from 0.2-2%. Once diagnosed, Barrett's esophagus is estimated to have an annual neoplastic transformation rate of 0.5% per patient. The highlights of the endoscopic diagnosis and treatment are reviewed here, as well as the screening and monitoring of this process.


Subject(s)
Adenocarcinoma/pathology , Barrett Esophagus/pathology , Esophageal Neoplasms/pathology , Esophagoscopy , Precancerous Conditions/pathology , Adenocarcinoma/epidemiology , Adenocarcinoma/surgery , Barrett Esophagus/epidemiology , Barrett Esophagus/surgery , Cell Transformation, Neoplastic/pathology , Disease Progression , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/surgery , Esophagectomy/methods , Esophagoscopy/methods , Humans , Incidence , Metaplasia , Precancerous Conditions/epidemiology , Precancerous Conditions/surgery , Predictive Value of Tests , Time Factors , Treatment Outcome
3.
Immunol Lett ; 155(1-2): 47-50, 2013.
Article in English | MEDLINE | ID: mdl-24113357

ABSTRACT

In the last few years the improvements of chemotherapy regimens and supportive care has progressively ameliorated the prognosis of children suffering from Acute Myeloid Leukemia (AML). However, a still high percentage of children do not respond to first line treatments or relapse and need to undergo further treatments. The need to explore new agents other than chemotherapy has been highlighted in the last years in order to overcome drug related resistance and toxicity. Recently, novel therapies have been studied within early phases pediatric trials and seem to show encouraging results. In fact, the knowledge of molecular abnormalities related to AML pathogenesis has permitted to identify selective drugs that may represent an important tool for the development of patient-tailored treatments. Nowadays, FLT3, Aurora Kinases, mTORS's and proteasome inhibitors represents the most promising drugs that are being used in pediatric AML studies.


Subject(s)
Leukemia, Myeloid, Acute/therapy , Molecular Targeted Therapy/trends , Aurora Kinase A/metabolism , Child , Clinical Trials as Topic , Humans , Leukemia, Myeloid, Acute/immunology , Precision Medicine , Proteasome Endopeptidase Complex/metabolism , TOR Serine-Threonine Kinases/metabolism , fms-Like Tyrosine Kinase 3/metabolism
5.
Oncogene ; 26(25): 3594-602, 2007 May 28.
Article in English | MEDLINE | ID: mdl-17530013

ABSTRACT

As a cancer immunotherapy tool, idiotypes (Ids) have been used in different ways over the last three decades, depending on the actual human tumor cell target. It all started with passive, monoclonal, anti-Id antibody treatment of B-cell lymphoma, a setting in which results were tantalizing, but logistics unsustainable. It then moved toward the development of anti-Id vaccines for the treatment of the same tumors, a setting in which we have recently provided the first formal proof of principle of clinical benefit associated with the use of a human cancer vaccine. Meanwhile, it also expanded in the direction of exploiting the antigenic mimicry of some Ids with Id-unrelated, tumor-associated antigens for the immunotherapy of a number of solid tumors, a setting in which clinical results are still far from being consolidated. All in all, over the years Id-based immunotherapy has paved the way for a number of seminal therapeutic improvements for cancer patients, including the development of most if not all Id-unrelated monoclonal antibodies that have recently revolutionized the field.


Subject(s)
Antibodies, Anti-Idiotypic/immunology , Antibodies, Anti-Idiotypic/therapeutic use , Immunotherapy , Neoplasms/immunology , Neoplasms/therapy , Animals , Antibodies, Neoplasm/immunology , Antibodies, Neoplasm/therapeutic use , Cancer Vaccines , Humans , Neoplasms/pathology
8.
Bone Marrow Transplant ; 35 Suppl 1: S89-92, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15812539

ABSTRACT

Aplastic anemia (AA) is a rare disease with a major autoimmune pathogenetic component. CTLA4 is a T-lymphocyte surface molecule involved in the maintenance of immune tolerance. Some polymorphisms associated with a reduced expression of CTLA4, and thus presumably with increased tendency to autoimmunity, have been associated with various autoimmune diseases. In this study, we evaluated the distribution of the low expression polymorphisms -318C > T and 49A > G of CTLA4 in a population of 67 patients with acquired AA and in 100 normal controls. There was no difference in the distribution of the tested polymorphism between patients and controls and, within the patient group, between those who responded to immunosuppression vs those who did not respond. This study indicates that the polymorphisms -318C > T and 49A > G of CTLA4 do not affect the risk of developing AA and do not influence the response to immunosuppression.


Subject(s)
Anemia, Aplastic/genetics , Antigens, Differentiation/genetics , Exons/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Adolescent , Adult , Antigens, CD , CTLA-4 Antigen , Case-Control Studies , Child , Child, Preschool , Female , Gene Expression Regulation , Genetic Predisposition to Disease , Humans , Infant , Male , Middle Aged , Risk Factors , White People
9.
Rev Med Univ Navarra ; 48(3): 14-23, 2004.
Article in Spanish | MEDLINE | ID: mdl-15622921

ABSTRACT

Cancer vaccines are conceived as therapeutic tools, in contrast to the prophylactic vaccines used to fight against infectious diseases. Among the most potent therapeutic vaccines, anti-idiotype vaccination is directed against the tumor idiotype, the only well-characterized tumor antigen displayed in neoplastic B-cells. Anti-idiotype vaccines have demonstrated clinical benefit against follicular lymphoma and are currently being evaluated in two different phase III clinical trials. Additional emerging strategies, which include the use of dendritic cells and the production of vaccines via molecular means will surely allow us to draw important conclusions concerning the treatment of cancer patients.


Subject(s)
Cancer Vaccines/immunology , Neoplasms/drug therapy , Clinical Trials as Topic , Forecasting , Humans , Immunoglobulin Idiotypes/immunology , Immunotherapy/trends , Neoplasms/immunology
10.
An Sist Sanit Navar ; 27(1): 45-62, 2004.
Article in Spanish | MEDLINE | ID: mdl-15146205

ABSTRACT

The continuous search for therapeutic approaches that improve the conventional treatments of neoplasms, together with an improved understanding of the immune system, has led in recent years to the development of Immunotherapy. Basically, a distinction can be made between two forms of immunotherapy: passive immunotherapy, which consists in the transfer of antibodies or cells previously generated in vitro that are directed against the tumour, and active immunotherapy, which attempts to activate in vivo the immune system and induce it to elaborate a specific response against the tumor antibodies. Hematological neoplasms, specifically some B lymphomas, express in their membrane an immunoglobulin that is considered a specific antigen of the tumour, which is why these diseases have become the ideal target for immunotherapy treatments. There are many alternatives, ranging from protein vaccines, which have already shown clinical benefits, to those of the second generation, which make use of the new techniques of molecular biology to increase the efficacy of the vaccines and obtain their production in a quicker and less costly way, but with which there are not yet definitive clinical results.


Subject(s)
Cancer Vaccines/therapeutic use , Immunotherapy, Active/methods , Lymphoma, Follicular/drug therapy , Clinical Trials as Topic , Dendritic Cells/immunology , Humans , Immunization, Passive , Lymphoma, Follicular/immunology
11.
An. sist. sanit. Navar ; 27(1): 45-62, ene. 2004. tab, ilus
Article in Es | IBECS | ID: ibc-32182

ABSTRACT

La continua búsqueda de abordajes terapéuticos que mejoren los tratamientos convencionales de las enfermedades neoplásicas junto con el mejor conocimiento del sistema inmunitario ha llevado en los últimos años al desarrollo de la inmunoterapia. Básicamente se pueden distinguir dos formas de inmunoterapia: la inmunoterapia pasiva, que consiste en la transferencia de anticuerpos o células previamente generados in vitro que se dirigen contra el tumor, y la inmunoterapia activa, que pretende activar in vivo el sistema inmunitario e inducirlo a elaborar una respuesta específica contra los antígenos tumorales. Las neoplasias hematológicas, concretamente algunos linfomas B, expresan en su membrana una inmunoglobulina que se considera un verdadero antígeno específico de tumor; por eso estas enfermedades se han convertido en la diana ideal de los tratamientos de inmunoterapia. Las alternativas son muchas, desde las vacunas proteicas que ya han demostrado beneficios clínicos, hasta las de segunda generación, que aprovechan las nuevas técnicas de biología molecular para aumentar la eficacia de las vacunas y conseguir su producción de forma más rápida y menos costosa, pero con las que todavía no hay resultados clínicos definitivos (AU)


Subject(s)
Immunotherapy, Active/methods , Immunotherapy, Active/trends , Immunotherapy, Active , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/therapy , Antibodies, Monoclonal/analysis , Antibodies, Monoclonal/isolation & purification , DNA/immunology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/therapy , Immune System/physiopathology , Molecular Biology/methods , Dendritic Cells/immunology , Dendritic Cells/pathology , Immunotherapy/classification
12.
Curr Gene Ther ; 2(1): 79-89, 2002 Feb.
Article in English | MEDLINE | ID: mdl-12108975

ABSTRACT

Bone marrow-derived dendritic cells have been used to treat established experimental tumors by unleashing a cellular immune response against tumor antigens. Such antigens are artificially loaded onto dendritic cells' antigen-presenting molecules by different techniques including incubation with synthetic antigenic determinants, tumor lysates or nucleic acids encoding for those relevant antigens. Ex vivo gene transfer with viral and non-viral vectors is frequently used to obtain expression of the tumor antigens and thereby to formulate the therapeutic vaccines. Efficacy of the approaches is greatly enhanced if dendritic cells are transfected with a number of genes which encode immunostimulating factors. In some cases, such as with IL-12, IL-7 and CD40L genes, injection inside experimental malignancies of thus transfected dendritic cells induces complete tumor regression in several models. In this case tumor antigens are captured by dendritic cells by still unclear mechanisms and transported to lymphoid organs where productive antigen presentation to T-cells takes place. Many clinical trials testing dendritic cell-based vaccines against cancer are in progress and partial clinical efficacy has been already proved. Transfection of genes further strengthening the immunogenicity of such strategies will join the clinical club soon.


Subject(s)
Cytokines/genetics , Gene Transfer Techniques , Genetic Therapy/methods , Neoplasms/therapy , Bone Marrow Cells/cytology , CD40 Ligand/genetics , Genetic Vectors , Humans , Interleukin-12/genetics , Interleukin-7/genetics , Models, Biological , Transfection , Viruses/genetics
14.
Inmunología (1987) ; 20(3): 130-142, jul. 2001. ilus, tab, graf
Article in En | IBECS | ID: ibc-12903

ABSTRACT

Las células dendríticas se vienen usando como adyuvantes naturales para inducir respuestas inmunitarias con utilidad terapéutica. Para conseguir esto, los genes que codifican para antígenos relevantes son transfectados en células dendríticas mediante vectores virales y no virales. Los adenovirus recombinantes defectivos que codifican para antígenos o citoquinas se utilizan con gran eficiencia para transfectar ex vivo células dendríticas. Aquí hemos estudiado los efectos de infectar células dendríticas humanas y murinas con adenovirus que codifican para el gen reportero -galactosidasa (AdCMVLacZ). La infección con AdCMVLacZ induce la translocación nuclear de diferentes factores de transcripción de la familia de NF -B, a través la inducción de fosforilación de I -B según se demuestra mediante geles de retardo de movilidad e inmunoblots. La activación de NF- B se indujo también con capsides virales semipurificadas o adenovirus sin transgén, pero no mediante un adenovirus que codifica para un inhibidor dominante negativo de I -B (AdCMVI -B). A diferencia de AdCMVI B , AdCMVLacZ induce aumentos en la expresión de CD40, CD80 y CD86 con aumentos menos significativos de MHC clase II. También induce la expresión de IL-6 pero no de TNF ni IL-12. Estos cambios hacen que las células dendríticas sean más eficientes en inducir proliferación en MLR alogénicos. Nuestros resultados muestran que los adenovirus recombinantes inducen de forma independiente de transgén, cambios en el status madurativo de células dendríticas humanas y murinas que son relevantes para sus funciones. (AU)


Subject(s)
Animals , Humans , Mice , Dendritic Cells/virology , NF-kappa B/metabolism , Adenoviridae , Defective Viruses , Adenoviridae/genetics , Dendritic Cells/physiology , Transcription Factors , beta-Galactosidase/genetics , beta-Galactosidase/metabolism , Mice, Inbred BALB C , Mice, Inbred C57BL , Bone Marrow Cells , Antigens, Surface/metabolism , Cytokines/metabolism , Phenotype , Defective Viruses/genetics , Recombination, Genetic
15.
Pediatr Infect Dis J ; 20(5): 495-501, 2001 May.
Article in English | MEDLINE | ID: mdl-11368106

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) is the major viral cause of severe respiratory infections in children younger than 2 years of age. Nevertheless there are not enough epidemiologic data about the role of RSV as a cause of infantile mortality from pneumonia, mainly in young children from developing countries Aim. To determine the frequency of RSV infection in lung tissue samples from Mexican children deceased with pneumonia, by reverse transcription (RT) and PCR. METHODS: Postmortem lung tissue samples from 98 children younger than 2 years of age who died of pneumonia during the period of 1989 to 1997 were studied. Paraffin was removed with xylene from 10-microm lung sections, the total RNA was extracted and complementary DNA was obtained by RT reaction. A nested PCR with the use of oligonucleotides specific for the F glycoprotein gene was developed. Samples negatives for RSV were tested for the absence of polymerase inhibitors and for complementary DNA integrity. RESULTS: Twenty-nine of the 98 (30%) children deceased with pneumonia were positive for RSV by RT-PCR; 8 were detected from 13 (62%) children with histopathologic diagnosis of viral pneumonia and 21 from 85 (25%) children with histopathologic diagnosis of bacterial pneumonia (P = 0.018). There was no significant difference in RSV infection according to age groups or seasonal pattern. CONCLUSIONS: RSV infection is frequent in Mexican children younger than 2 years of age who died of pneumonia. Although RSV was more common in viral pneumonia, mixed infections with RSV and bacterial pneumonia were also common.


Subject(s)
Lung/microbiology , Pneumonia, Bacterial/pathology , Respiratory Syncytial Virus Infections/pathology , Respiratory Syncytial Viruses/isolation & purification , Autopsy , Cross-Sectional Studies , Female , Humans , Infant , Lung/pathology , Male , Mexico , Polymerase Chain Reaction , RNA, Viral/analysis , Retrospective Studies
16.
Exp Hematol ; 29(5): 589-95, 2001 May.
Article in English | MEDLINE | ID: mdl-11376871

ABSTRACT

OBJECTIVE: With the aim of obtaining monoclonal antibodies (mAbs) against mouse endothelial surface antigens, immunization of rats with a mouse-derived endothelial cell line (PY4.1) and subsequent hybridoma production were performed. MATERIALS AND METHODS: One of the mAbs produced by hybridoma EOL5F5 was selected for its surface binding to endothelial cell lines, and identification of the mAb-recognized antigen was performed by immunoprecipitation. Experiments were performed to analyze the effects of EOL5F5 on systemic administration to mice. RESULTS: EOL5F5-recognized antigen was a single band of 35 kDa under reducing and nonreducing conditions, features that do not match other known differentiation antigens with comparable tissue distribution. In vivo administration of purified EOL5F5 mAb to mice (n = 20) induced intense cutaneous purpura as well as severe but transient thrombocytopenia. Expression of EOL5F5-recognized antigen was detected on platelets from which it immunoprecipitated a moiety of identical electrophoretic pattern in SDS-PAGE, as the one recognized on endothelial cells. Immunohistochemically, EOL5F5-recognized antigen (p35) also was expressed on dermal capillaries, suggesting that, in addition to thrombocytopenia, damaging effects of the antibody on endothelial cells also might cause the observed purpura. CONCLUSIONS: Our results show induction of thrombocytopenic purpura in mice with an mAb against a single antigenic determinant expressed on both platelets and endothelium. EOL5F5 mAb injection sets the stage for useful experimental models that resemble immune thrombocytopenic purpura.


Subject(s)
Antibodies, Monoclonal/toxicity , Antigens, Differentiation/immunology , Antigens, Surface/immunology , Blood Platelets/immunology , Endothelium, Vascular/immunology , Purpura, Thrombocytopenic/etiology , Animals , Antibodies, Monoclonal/immunology , Epitopes/immunology , Hybridomas/immunology , Immunization , Mice , Mice, Nude , Purpura, Thrombocytopenic/immunology , Rats , Rats, Wistar , Skin/blood supply , Thrombocytopenia/etiology
17.
Gene Ther ; 8(4): 259-67, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11313799

ABSTRACT

Despite the efficacy of IL-12 in cancer experimental models, clinical trials with systemic recombinant IL-12 showed unacceptable toxicity related to endogenous IFNgamma production. We report that systemic administration of a recombinant adenovirus encoding IL-12 (AdCMVmIL-12) has a dramatically different survival outcome in a number of mouse pure strains over a wide range of doses. For instance at 2.5 x 10(9) p.f.u., systemic AdCMVmIL-12 killed all C57BL/6 mice but spared all BALB/c mice. Much higher IFNgamma concentrations in serum samples of C57BL/6 than in those from identically treated BALB/c were found. Causes for heterogeneous toxicity can be traced to differences among murine strains in the levels of gene transduction achieved in the liver, as assessed with adenovirus coding for reporter genes. In accordance, IL-12 serum concentrations are higher in susceptible mice. In addition, sera from C57BL/6 mice treated with AdCMVmIL-12 showed higher levels of IL-18, a well-known IFNgamma inducer. Interestingly, lethal toxicity in C57BL/6 mice was abolished by administration of blocking anti-IFNgamma mAbs and also by simultaneous depletion of T cells, NK cells, and macrophages. These observations together with the great dispersion of IFNgamma produced by human PBMCs upon in vitro stimulation with IL-12, or infection with recombinant adenovirus encoding IL-12, suggest that patients might also show heterogeneous degrees of toxicity in response to IL-12 gene transfer.


Subject(s)
Adenoviridae/genetics , Genetic Therapy/adverse effects , Genetic Vectors/adverse effects , Interleukin-12/genetics , Transduction, Genetic , Animals , Antibodies, Monoclonal/pharmacology , Cells, Cultured , Genetic Vectors/genetics , Humans , Interferon-gamma/blood , Interferon-gamma/immunology , Interferon-gamma/pharmacology , Interleukin-12/blood , Killer Cells, Natural/immunology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Liver/immunology , Macrophages/immunology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred DBA , Recombinant Proteins , Species Specificity , T-Lymphocytes/immunology
18.
Rev. Rol enferm ; 24(2): 145-147, feb. 2001. ilus, tab
Article in Es | IBECS | ID: ibc-25392

ABSTRACT

Se analizan las cargas de trabajo de enfermería, cuantificadas en tiempo, en pacientes intervenidos de aneurisma aortoabdominal por vía programada (sin llegar a la rotura del aneurisma), y por vía urgente (con aneurisma roto). Todo ello desde el punto de vista de la desconexión de la ventilación mecánica. Se concluye que el tiempo de ventilación mecánica en el grupo urgente es 12,8 veces mayor que en el programado (AU)


Subject(s)
Humans , Workload/statistics & numerical data , Nursing Care/statistics & numerical data , Ventilator Weaning/nursing , Aortic Aneurysm, Abdominal/nursing , Respiration, Artificial/nursing , Aneurysm, Ruptured/nursing , Emergency Nursing/methods
19.
Ann Oncol ; 12(10): 1479-84, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11762822

ABSTRACT

BACKGROUND: The complementarity determining region 3 (CDR3) of the immunoglobulin (Ig) heavy chain variable region (VH) is the most reliable molecular fingerprint for most if not all human B cells. The nucleotide sequence encoding for any B-cell tumor-specific VH CDR3 is currently identified by PCR sequencing based on procedures involving the usage of either radioactive materials, patient/family-specific primers, or bacterial cloning. PATIENTS AND METHODS: In six consecutive patients with follicular lymphoma we assessed the feasibility of a method that allows for identification of the tumor-specific VH CDR3 using consensus primers while avoiding both radioactive materials and bacterial cloning procedures. RESULTS: The tumor-specific VH CDR3 was successfully identified in all six patients in nearly half the time typically required by any other method currently utilized. The feasibility of the proposed method was not significantly affected either by the tumor-specific Ig isotype, or by the tumor infiltration in the original biopsy specimen. In the three patients for whom tumor specimen-derived hybridomas were available, the tumor-specific VH CDR3 was also found in at least 8 of 10 of them. CONCLUSIONS: The proposed method allows the ability to quickly identify the B-cell tumor-specific VH CDR3 using consensus primers while avoiding radioactive materials and bacterial cloning procedures.


Subject(s)
Biomarkers, Tumor/analysis , DNA Fingerprinting , DNA, Neoplasm/analysis , Immunoglobulin Heavy Chains/genetics , Lymphoma, B-Cell/genetics , Lymphoma, Follicular/genetics , Base Sequence , DNA Primers , DNA, Complementary , Humans , Hybridomas , Lymphoma, B-Cell/pathology , Lymphoma, Follicular/pathology , Molecular Sequence Data , Polymerase Chain Reaction , Sensitivity and Specificity , Sequence Analysis, DNA , Software , Time Factors
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