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1.
S Afr J Surg ; 62(2): 23-27, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38838115

RESUMEN

BACKGROUND: Hepatic inflammatory myofibroblastic tumours (HIMTs) are rare and poorly described in the literature. Most publications are single patient case reports and lack detailed reporting on characteristics, management, and outcomes. This systematic review aimed to assess the demography, clinical presentation, typical imaging features, histopathology, treatment, and outcomes of patients presenting with HIMTs. METHODS: A systematic literature search was performed in MEDLINE (PubMed), EMBASE (Scopus), JSTOR, Cochrane CENTRAL (Cochrane Library), and the databases included in the Web of Science for studies published between 1940 and 2023 on HIMTs, including its reported synonyms. Case series or cohort studies that reported on the management and outcomes of at least four patients with histologically confirmed HIMTs were included in the analysis. RESULTS: After screening 4553 publications, 22 articles including a total of 440 patients with confirmed HIMTs were eligible for inclusion. The average age was 53.4 years (range 42.0-65.0) with a male to female ratio of 1.7:1. Abdominal pain, discomfort, fever, and loss of weight were the most common presenting symptoms. Surgical resection is the standard of care for HIMTs and is associated with low mortality of 3.4% and low disease recurrence. CONCLUSION: HIMT is a disease more often affecting middle-aged males. The lesions are typically solitary with low recurrence after treatment. The relative roles of surgical versus medical treatment remain unclear. Differences in clinical presentation, histopathology, and treatment of HIMTs compared to inflammatory myofibroblastic tumour (IMT) at extrahepatic sites could challenge the current view of IMT as a single pathological entity.


Asunto(s)
Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirugía , Granuloma de Células Plasmáticas/cirugía , Granuloma de Células Plasmáticas/patología , Granuloma de Células Plasmáticas/diagnóstico , Masculino , Neoplasias de Tejido Muscular/cirugía , Neoplasias de Tejido Muscular/patología , Neoplasias de Tejido Muscular/diagnóstico , Femenino , Persona de Mediana Edad
2.
Oncogene ; 32(6): 689-98, 2013 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-22410775

RESUMEN

Deregulation of the receptor tyrosine kinase Axl has been implicated in the progression of several human cancers. However, the role of Axl in prostate cancer remains poorly understood, and the therapeutic efficacy of Axl targeting remains untested. In this report we identified Axl as a new therapeutic target for prostate cancer. Axl is consistently overexpressed in prostate cancer cell lines and human prostate tumors. Interestingly, the blockage of Axl gene expression strongly inhibits proliferation, migration, invasion and tumor growth. Furthermore, inhibition of Axl expression by small interfering RNA regulates a transcriptional program of genes involved in cell survival, strikingly all connected to the nuclear factor-κB pathway. Additionally, blockage of Axl expression leads to inhibition of Akt, IKKα and IκBα phosphorylation, increasing IκBα expression and stability. Furthermore, induction of Akt phosphorylation by insulin-like growth factor 1 in Axl knockdown cells restores Akt activity and proliferation. Taken together, our results establish an unambiguous role for Axl in prostate cancer tumorigenesis with implications for prostate cancer treatment.


Asunto(s)
Transformación Celular Neoplásica , Neoplasias de la Próstata/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Terapia Molecular Dirigida , FN-kappa B/metabolismo , Metástasis de la Neoplasia , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Transducción de Señal , Regulación hacia Arriba , Tirosina Quinasa del Receptor Axl
3.
Curr Mol Med ; 12(5): 634-51, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22515981

RESUMEN

The Growth Arrest and DNA Damage-inducible 45 (GADD45) proteins have been implicated in regulation of many cellular functions including DNA repair, cell cycle control, senescence and genotoxic stress. However, the pro-apoptotic activities have also positioned GADD45 as an essential player in oncogenesis. Emerging functional evidence implies that GADD45 proteins serve as tumor suppressors in response to diverse stimuli, connecting multiple cell signaling modules. Defects in the GADD45 pathway can be related to the initiation and progression of malignancies. Moreover, induction of GADD45 expression is an essential step for mediating anti-cancer activity of multiple chemotherapeutic drugs and the absence of GADD45 might abrogate their effects in cancer cells. In this review, we present a comprehensive discussion of the functions of GADD45 proteins, linking their regulation to effectors of cell cycle arrest, DNA repair and apoptosis. The ramifications regarding their roles as essential and central players in tumor growth suppression are also examined. We also extensively review recent literature to clarify how different chemotherapeutic drugs induce GADD45 gene expression and how its up-regulation and interaction with different molecular partners may benefit cancer chemotherapy and facilitate novel drug discovery.


Asunto(s)
Transformación Celular Neoplásica/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias/metabolismo , Animales , Apoptosis/genética , Apoptosis/fisiología , Puntos de Control del Ciclo Celular/genética , Puntos de Control del Ciclo Celular/fisiología , Transformación Celular Neoplásica/genética , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias/genética , Proteinas GADD45
4.
Leukemia ; 23(5): 892-9, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19158832

RESUMEN

We found that composition of cell subsets within the CD34+ cell population is markedly altered in chronic phase (CP) chronic myeloid leukemia (CML). Specifically, proportions and absolute cell counts of common myeloid progenitors (CMP) and megakaryocyte-erythrocyte progenitors (MEP) are significantly greater in comparison to normal bone marrow whereas absolute numbers of hematopoietic stem cells (HSC) are equal. To understand the basis for this, we performed gene expression profiling (Affymetrix HU-133A 2.0) of the distinct CD34+ cell subsets from six patients with CP CML and five healthy donors. Euclidean distance analysis revealed a remarkable transcriptional similarity between the CML patients' HSC and normal progenitors, especially CMP. CP CML HSC were transcriptionally more similar to their progeny than normal HSC to theirs, suggesting a more mature phenotype. Hence, the greatest differences between CP CML patients and normal donors were apparent in HSC including downregulation of genes encoding adhesion molecules, transcription factors, regulators of stem-cell fate and inhibitors of cell proliferation in CP CML. Impaired adhesive and migratory capacities were functionally corroborated by fibronectin detachment analysis and transwell assays, respectively. Based on our findings we propose a loss of quiescence of the CML HSC on detachment from the niche leading to expansion of myeloid progenitors.


Asunto(s)
Regulación Leucémica de la Expresión Génica/genética , Células Madre Hematopoyéticas/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Células Progenitoras Mieloides/patología , Adhesión Celular , Diferenciación Celular , Movimiento Celular , Proliferación Celular , Técnica del Anticuerpo Fluorescente , Perfilación de la Expresión Génica , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Células Madre Neoplásicas , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
5.
Biochim Biophys Acta ; 1770(8): 1259-65, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17574764

RESUMEN

In this study, we evaluated the NTPDases and ecto-5'-nucleotidase (CD73) expression profiles and the pattern of adenine nucleotide hydrolysis in rats submitted to the Walker 256 tumor model, 6, 10 and 15 days after the subcutaneous inoculation. Using RT-PCR analysis, we identified mRNA for all of the members of the ecto-nucleoside triphosphate diphosphohydrolase family investigated and a 5'-nucleotidase. By quantitative real-time PCR, Entpd1 (Cd39) and Entpd2 (Cd39L1) and CD73 were identified as the dominant genes expressed by the Walker 256 tumor, at all times studied. Extracellular adenine nucleotide hydrolysis by the Walker 256 tumor was estimated by HPLC analysis. Rapid hydrolysis of extracellular ATP by the tumor cells was observed, leading to the formation of adenosine and inosine in cells obtained from solid tumors at 6 and 10 days after inoculation. Cells obtained from solid tumors at 15 days of growth presented high levels of AMP and presented adenosine as a final product after 90 min of incubation. Results demonstrate that the presence of NTPDases and 5'-nucleotidase enzymes in Walker 256 tumor cells may be important for regulation of the extracellular adenine nucleotides/adenine nucleoside ratio, therefore leading to tumor growth.


Asunto(s)
5'-Nucleotidasa/metabolismo , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfato/metabolismo , Antígenos CD/metabolismo , Apirasa/metabolismo , Carcinoma 256 de Walker/enzimología , Animales , Línea Celular Tumoral , Masculino , Ratas , Ratas Wistar
6.
Neuroscience ; 138(2): 421-32, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16414200

RESUMEN

Inflammatory and degenerative pathophysiological processes within the CNS are important causes of human disease. Astrocytes appear to modulate these reactions and are a major source of inflammatory mediators, e.g. extracellular adenine nucleotides, in nervous tissues. Actions following extracellular nucleotides binding to type 2 purinergic receptors are regulated by ectonucleotidases, including members of the CD39/ecto-nucleoside triphosphate diphosphohydrolase family. The ectonucleotidases of astrocytes expressed by rat brain rapidly convert extracellular ATP to ADP, ultimately to AMP. RT-PCR, immunocytochemistry as well as Western blotting analysis demonstrated expression of multiple ecto-nucleoside triphosphate diphosphohydrolase family members at both the mRNA and protein level. By quantitative real-time PCR, we identified Entpd2 (CD39L1) as the dominant Entpd gene expressed by rat hippocampal, cortical and cerebellar astrocytes. These data in combination with the elevated ecto-ATPase activity observed in these brain regions, suggest that NTPDase2, an ecto-enzyme that preferentially hydrolyzes ATP, is the major ecto-nucleoside triphosphate diphosphohydrolase expressed by rat astrocytes. NTPDase2 may modulate inflammatory reactions within the CNS and could represent a useful therapeutic target in human disease.


Asunto(s)
Adenosina Trifosfatasas/genética , Astrocitos/enzimología , Adenosina Difosfato/metabolismo , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Encéfalo/enzimología , Cinética , Ratas , Proteínas Recombinantes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Especificidad por Sustrato , Transfección
7.
Biochem Biophys Res Commun ; 296(4): 897-903, 2002 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-12200132

RESUMEN

Adenoviruses have been used for gene therapy or immunization due to their ability to efficiently infect a broad range of cells and tissues. These applications as well as specificity could be improved further by redirecting binding of the virus to specific cell types. In this regard, modification of viral genes encoding coat proteins is an option to achieve improvement in retargeting. In this report, we describe a substitution in the adenovirus type 2 fiber globular region by the 44 amino acid C4 domain of human immunodeficiency virus type 1 gp120. In vitro translation analysis and immunoprecipitation assays show that the incorporation of the C4 domain into the fiber protein does not ablate its trimerization property and demonstrates the availability of the C4 epitope for interaction with monoclonal anti-C4 antibody. The recombinant adenovirus containing this modified fiber was also characterized by immunoprecipitation with the same antibody, showing the viability of such kind of modification.


Asunto(s)
Adenoviridae/metabolismo , Cápside/química , Adenoviridae/química , Línea Celular , Epítopos , Genoma Viral , Proteína gp120 de Envoltorio del VIH/metabolismo , Ligandos , Modelos Biológicos , Reacción en Cadena de la Polimerasa , Pruebas de Precipitina , Unión Proteica , Biosíntesis de Proteínas , Estructura Terciaria de Proteína , Recombinación Genética , Transcripción Genética
8.
J Clin Microbiol ; 35(11): 2958-63, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9350767

RESUMEN

Seventy-four E. coli strains isolated from piglets with diarrhea or edema disease in Spain were serotyped and examined for production of heat-labile (LT) and heat-stable (ST) enterotoxins (LT-I, LT-II, STaH, STaP, and STb) and verotoxins (VT1, VT2, and VT2v = VTe) by phenotypic (Vero cell assay and infant mouse test) and genotypic (colony hybridization and PCR) methods. In general, an excellent correlation was found between the results obtained with a PCR approach and those determined with biological assays. DNA probes used in the hybridization also showed a very good agreement with phenotypic results, with the exception of a VT1 probe that initially produced 10 false-positive reactions. The gene coding for STb (58 strains) was the most prevalent gene detected by PCR, followed by those coding for STa (46 strains), LT (19 strains), VT2v (11 strains), and VT1 (1 strain). Apparently, in Spain three seropathotypes are predominant: (i) O149:K91:H10 K88+ LT-I+ STb+, (ii) O141:K85ab:H- P987+ STaP+, and (iii) O138:K81:H14 or H- STaP+ VT2v+. We conclude that PCR is a fast, specific, and practical method for the identification of enterotoxin and VT genes in clinical and epidemiological studies.


Asunto(s)
Enterotoxinas/biosíntesis , Infecciones por Escherichia coli/veterinaria , Proteínas de Escherichia coli , Escherichia coli/genética , Enfermedades de los Porcinos , Animales , Toxinas Bacterianas/biosíntesis , Chlorocebus aethiops , Diarrea/microbiología , Diarrea/veterinaria , Edema , Escherichia coli/clasificación , Escherichia coli/fisiología , Infecciones por Escherichia coli/microbiología , Genes Bacterianos , Genotipo , Ratones , Fenotipo , Serotipificación , Toxina Shiga I , Toxina Shiga II , Porcinos , Células Vero
9.
Vet Microbiol ; 42(2-3): 105-10, 1994 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7886925

RESUMEN

Forty-six verotoxin-producing Escherichia coli (VTEC) strains isolated from diarrhoeic and healthy calves in Spain were examined for DNA sequences homologous to genes for verotoxins (VT1 and VT2) and enterotoxins (LT-I, LT-II, STaH, STaP and STb). Hybridisation showed that 26 (57%) of VTEC strains carried VT1 genes, 13 (28%) possessed VT2 genes, and 7 (15%) carried both VT1 and VT2 genes. No VTEC strains hybridised with DNA probes for enterotoxins. A correlation was found between the serotype and type of VT produced. Thus, all strains of serotypes O26:K-:H11 (13 strains), O103:K-:H2 (3 strains) and O128:K?:H- (4 strains) hybridised with the VT1 probe only, whereas all strains of serotypes O4:K-:H4 (3 strains) and O113:K-:H21 (4 strains) were positive with the VT2 probe only. By contrast, O81:K?:H28 (2 strains) and O157:K-:H- (2 strains) strains hybridised with both VT1 and VT2 probes. One strain of serotype O157:K-:H7 was VT2 positive.


Asunto(s)
Toxinas Bacterianas/biosíntesis , Toxinas Bacterianas/genética , Bovinos/microbiología , Escherichia coli/genética , Genes Bacterianos , Animales , Enfermedades de los Bovinos/microbiología , Sondas de ADN , Diarrea/microbiología , Diarrea/veterinaria , Reservorios de Enfermedades , Enterotoxinas/genética , Escherichia coli/clasificación , Escherichia coli/patogenicidad , Humanos , Serotipificación , Toxina Shiga I , Toxina Shiga II , España
10.
Braz J Med Biol Res ; 27(3): 623-6, 1994 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8081286

RESUMEN

The 18-kDa protein from Mycobacterium leprae is a major target for the immune response in leprosy. We have developed a system to express this antigen in yeast as a fusion protein with the C-terminal region of the yeast membrane protein GAS1, which would render the recombinant protein anchored to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. Cells lacking the GAS1 gene and transformed with the hybrid 18-kDa-GAS1 construct express a polypeptide that reacts with an 18-kDa-specific monoclonal antibody. In addition, these cells react with an alpha-CRD antibody after GPI-PLC treatment. The non-transformed cells are negative. These data indicate that our system may be suitable for the expression of foreign proteins in yeast in a GPI-anchored form.


Asunto(s)
Proteínas Bacterianas/genética , Glicosilfosfatidilinositoles/genética , Mycobacterium leprae/inmunología , Proteínas de Saccharomyces cerevisiae , Proteínas Bacterianas/inmunología , Proteínas Fúngicas/genética , Genes Fúngicos , Vectores Genéticos , Glicosilfosfatidilinositoles/inmunología , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/inmunología , Mycobacterium leprae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/inmunología
11.
Braz. j. med. biol. res ; 27(3): 623-6, Mar. 1994. ilus
Artículo en Inglés | LILACS | ID: lil-148934

RESUMEN

The 18-kDa protein from Mycobacterium leprae is a major target for the immune response in leprosy. We have developed a system to express this antigen in yeast as a fusion protein with the C-terminal region of the yeast membrane protein GAS1, which would render the recombinant protein anchored to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. Cells lacking the GAS1 gene and transformed with the hybrid 18-kDa-GAS1 construct express a polypeptide that reacts with an 18-kDa-specific monoclonal antibody. In addition, these cells react with an alpha-CRD antibody after GPI-PLC treatment. The non-transformed cells are negative. These data indicate that our system may be suitable for the expression of foreign proteins in yeast in a GPI-anchored form


Asunto(s)
Glicosilfosfatidilinositoles/genética , Mycobacterium leprae/inmunología , Proteínas Bacterianas/genética , Genes Fúngicos , Vectores Genéticos , Glicosilfosfatidilinositoles/inmunología , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/inmunología , Mycobacterium leprae/genética , Proteínas Bacterianas/inmunología , Proteínas Fúngicas/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/inmunología
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