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1.
Ann Oncol ; 29(3): 737-743, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29267856

RESUMEN

Background: Health-related quality of life (HRQoL) was a secondary end point in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient-centered end points. Patients and methods: HRQoL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified end points included mean differences in HRQoL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQoL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6 months with PZ. Results: There were statistically significant differences between PZ and P in QLQ-C30 global health status [5.5 points; 95% confidence interval (CI), 0.7-10.4, P = 0.024] from baseline to 25 months, but not EQ-5D-3L (0.018 points; 95% CI - 0.033 to 0.069, P = 0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI 3.6-12.5, P = 0.001). QAPFS was 386 days (95% CI 366-404 days) with PZ versus 359 days (95% CI 338-379 days) with placebo (P = 0.052). PD was associated with a decline in HRQoL (P < 0.0001). Median time to second-line chemotherapy was 19.7 months with PZ and 15.0 months with P [hazard ratio (HR) 0.72, 95% CI 0.69-0.86, P = 0.0001]. Conclusions: There were small to no significant mean score differences in global HRQoL and EQ5D-3L between PZ and placebo, respectively, despite the increased toxicity of PZ. Exploratory end points including QAPFS, impact of specific symptoms on HRQoL during treatment and at PD help place the PFS gain with PZ in context and interpret the results. Additional patient-centered end points should be considered in trials of maintenance therapy in EOC beyond mean differences in HRQoL scores alone, to support the benefit to patients of prolongation of PFS. Clinical Trials Registration Number: NCT00866697.


Asunto(s)
Antineoplásicos/efectos adversos , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Quimioterapia de Mantención/efectos adversos , Neoplasias Ováricas/tratamiento farmacológico , Pirimidinas/efectos adversos , Calidad de Vida , Sulfonamidas/efectos adversos , Adulto , Inhibidores de la Angiogénesis/efectos adversos , Método Doble Ciego , Femenino , Humanos , Indazoles , Quimioterapia de Mantención/métodos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Supervivencia sin Progresión , Tiempo de Tratamiento
2.
Arch Womens Ment Health ; 21(3): 365-374, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29264646

RESUMEN

This study aimed to investigate prospectively the contribution of maternal physical health and/or breastfeeding problems to maternal mood (depression, anxiety, fatigue, irritability, confusion, vigor) at 8-weeks postpartum. A prospective study was conducted. Participants were recruited antenatally from a public and a private maternity hospital in Melbourne, Australia. Nulliparous pregnant women (N = 229), ≥ 18 years of age, ≥ 36-week gestation, singleton pregnancy and with sufficient English were eligible. Data were collected by self-report questionnaire (pregnancy, weeks 1-4 postpartum) and telephone interview (week 8 postpartum). A high burden of physical problems was classified as ≥ 3 problems (caesarean/perineal pain; back pain; constipation; haemorrhoids; urinary and bowel incontinence) for ≥ 2 time points. A high burden of breastfeeding problems was having ≥ 2 problems (mastitis; nipple pain; frequent expressing; over- or under-supply of milk) for ≥ 2 time points. Multivariate linear regression was used to investigate the relationship between maternal mood, assessed using Profile of Mood States (8-week postpartum), and a high burden of breastfeeding and/or physical health problems. Forty-six women (20.1%) had a high burden of physical symptoms, 44 (19.2%) a high burden of breastfeeding problems only and 25 women (11.0%) had both. A high burden of breastfeeding problems alone (ß = 10.6, p = 0.01) or with co-morbid physical problems (ß = 15.35, p = 0.002) was significantly associated with poorer maternal mood at 8 weeks. Early, effective postnatal treatment of maternal health and breastfeeding problems could reduce women's risk for poor mental health.


Asunto(s)
Lactancia Materna/psicología , Depresión Posparto/psicología , Conducta Materna/psicología , Salud Materna , Trastornos del Humor/psicología , Depresión Posparto/epidemiología , Femenino , Estado de Salud , Humanos , Edad Materna , Trastornos del Humor/epidemiología , Periodo Posparto , Estudios Prospectivos , Adulto Joven
3.
Clin Exp Immunol ; 187(1): 113-123, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27667787

RESUMEN

Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4+ T cells. Lack of interleukin (IL)-12p70 production is a key immunoregulatory attribute of tolDC but does not explain their action fully. Here we show that tolDC express transforming growth factor (TGF)-ß1 at both mRNA and protein levels, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte-derived DC. By inhibiting TGF-ß1 signalling we demonstrate that tolDC regulate CD4+ T cell responses in a manner that is at least partly dependent upon this cytokine. Crucially, we also show that while there is no significant difference in expression of TGF-ßRII on CD4+ T cells from RA patients and healthy controls, RA patient CD4+ T cells are measurably less responsive to TGF-ß1 than healthy control CD4+ T cells [reduced TGF-ß-induced mothers against decapentaplegic homologue (Smad)2/3 phosphorylation, forkhead box protein 3 (FoxP3) expression and suppression of (IFN)-γ secretion]. However, CD4+ T cells from RA patients can, nonetheless, be regulated efficiently by tolDC in a TGF-ß1-dependent manner. This work is important for the design and development of future studies investigating the potential use of tolDC as a novel immunotherapy for the treatment of RA.


Asunto(s)
Artritis Reumatoide/terapia , Linfocitos T CD4-Positivos/inmunología , Células Dendríticas/inmunología , Tolerancia Inmunológica , Inmunoterapia/métodos , Factor de Crecimiento Transformador beta1/metabolismo , Artritis Reumatoide/inmunología , Células Cultivadas , Colecalciferol/farmacología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/trasplante , Dexametasona/farmacología , Factores de Transcripción Forkhead/metabolismo , Humanos , Inmunomodulación , Interleucina-12/genética , Interleucina-12/metabolismo , Activación de Linfocitos , Proteína Smad2/metabolismo
4.
J Fish Biol ; 89(3): 1866-72, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27329496

RESUMEN

In this study, population level lateralisation and the suitability of mirror tests as a test of natural aggressive behaviour in male rainbow kribs Pelvicachromis pulcher was investigated. Aggressive behaviour in live agonistic trials correlated positively with behaviours towards a mirror image and no visual lateralisation was detected.


Asunto(s)
Conducta Agonística , Cíclidos , Agresión , Animales , Masculino
5.
Ann Rheum Dis ; 74(2): 341-6, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24285491

RESUMEN

AIM: To assess whether in early (rheumatoid) arthritis (RA) patients, metacarpal bone mineral density (BMD) loss after 4 months predicts radiological progression after 1 year of antirheumatic treatment. METHODS: Metacarpal BMD was measured 4 monthly during the first year by digital X-ray radiogrammetry (DXR-BMD) in patients participating in the IMPROVED study, a clinical trial in 610 patients with recent onset RA (2010 criteria) or undifferentiated arthritis, treated according to a remission (disease activity score<1.6) steered strategy. With Sharp/van der Heijde progression ≥0.5 points after 1 year (yes/no) as dependent variable, univariate and multivariate logistic regression analyses were performed. RESULTS: Of 428 patients with DXR-BMD results and progression scores available, 28 (7%) had radiological progression after 1 year. Independent predictors for radiological progression were presence of baseline erosions (OR (95% CI) 6.5 (1.7 to 25)) and early DXR-BMD loss (OR (95% CI) 1.5 (1.1 to 2.0)). In 366 (86%) patients without baseline erosions, early DXR-BMD loss was the only independent predictor of progression (OR (95% CI) 2.0 (1.4 to 2.9)). CONCLUSIONS: In early RA patients, metacarpal BMD loss after 4 months of treatment is an independent predictor of radiological progression after 1 year. In patients without baseline erosions, early metacarpal BMD loss is the main predictor of radiological progression.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Densidad Ósea , Huesos del Metacarpo/diagnóstico por imagen , Absorciometría de Fotón , Artritis Reumatoide/patología , Progresión de la Enfermedad , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Prednisona/uso terapéutico , Sulfasalazina/uso terapéutico
6.
Pathologe ; 36(4): 372-84, 2015 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-26175197

RESUMEN

Chronic myeloid leukemia (CML) is diagnostically defined by the reciprocal translocation t(9;22)(q34;q11). This aberration can be detected by the BCR-ABL fluorescence in situ hybridization (FISH) technique. This article presents a comparative analysis of different commercially available FISH probes and different FISH protocols in order to optimize this technique on formalin-fixed and paraffin-embedded bone marrow trephine biopsies.


Asunto(s)
Médula Ósea/patología , Proteínas de Fusión bcr-abl/análisis , Proteínas de Fusión bcr-abl/genética , Hibridación Fluorescente in Situ/métodos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Biopsia con Aguja , Cromosomas Humanos Par 22 , Cromosomas Humanos Par 9 , Humanos , Hibridación Fluorescente in Situ/instrumentación , Sensibilidad y Especificidad , Translocación Genética
7.
Ann Rheum Dis ; 73(7): 1356-61, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23716067

RESUMEN

OBJECTIVES: To assess which treatment strategy is most effective in inducing remission in early (rheumatoid) arthritis. METHODS: 610 patients with early rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) started treatment with methotrexate (MTX) and a tapered high dose of prednisone. Patients in early remission (Disease Activity Score <1.6 after 4 months) tapered prednisone to zero and those with persistent remission after 8 months, tapered and stopped MTX. Patients not in early remission were randomised to receive either MTX plus hydroxychloroquine plus sulfasalazine plus low-dose prednisone (arm 1) or to MTX plus adalimumab (ADA) (arm 2). If remission was present after 8 months both arms tapered to MTX monotherapy; if not, arm 1 changed to MTX plus ADA and arm 2 increased the dose of ADA. Remission rates and functional and radiological outcomes were compared between arms and between patients with RA and those with UA. RESULTS: 375/610 (61%) patients achieved early remission. After 1 year 68% of those were in remission and 32% in drug-free remission. Of the randomised patients, 25% in arm 1 and 41% in arm 2 achieved remission at year 1 (p<0.01). Outcomes were comparable between patients with RA and those with UA. CONCLUSIONS: Initial MTX and prednisone resulted in early remission in 61% of patients with early (rheumatoid) arthritis. Of those, 68% were in remission and 32% were in drug-free remission after 1 year. In patients not in early remission, earlier introduction of ADA resulted in more remission at year 1 than first treating with disease-modifying antirheumatic drug combination therapy plus prednisone.


Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Metotrexato/uso terapéutico , Prednisona/uso terapéutico , Sulfasalazina/uso terapéutico , Adalimumab , Adulto , Anciano , Artritis/diagnóstico por imagen , Artritis/tratamiento farmacológico , Artritis Reumatoide/diagnóstico por imagen , Progresión de la Enfermedad , Quimioterapia Combinada/métodos , Intervención Médica Temprana/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Inducción de Remisión/métodos , Método Simple Ciego , Resultado del Tratamiento
8.
Anal Chem ; 85(15): 7139-45, 2013 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-23799655

RESUMEN

Expression microdissection (xMD) is a high-throughput, operator-independent technology that enables the procurement of specific cell populations from tissue specimens. In this method, histological sections are first stained for cellular markers via either chemical or immuno-guided methods, placed in close contact with an ethylene vinyl acetate (EVA) film, and exposed to a light source. The focal, transient heating of the stained cells or subcellular structures melts the EVA film selectively to the targets for procurement. In this report, we introduce a custom-designed flashcube system that permits consistent and reproducible microdissection of nuclei across an FFPE rat brain tissue section in milliseconds. In addition, we present a method to efficiently recover and combine captured proteins from multiple xMD films. Both light and scanning electron microscopy demonstrated captured nuclear structures. Shotgun proteomic analysis of the samples showed a significant enrichment in nuclear localized proteins, with an average 25% of recovered proteins localized to the nucleus, versus 15% for whole tissue controls (p < 0.001). Targeted mass spectrometry using multiple reaction monitoring (MRM) showed more impressive data, with a 3-fold enrichment in histones, and a concurrent depletion of proteins localized to the cytoplasm, cytoskeleton, and mitochondria. These data demonstrate that the flashcube-xMD technology is applicable to the proteomic study of a broad range of targets in molecular pathology.


Asunto(s)
Encéfalo/citología , Núcleo Celular/metabolismo , Microdisección/métodos , Proteómica/métodos , Secuencia de Aminoácidos , Animales , Precipitación Química , Formaldehído/metabolismo , Espectrometría de Masas , Datos de Secuencia Molecular , Adhesión en Parafina , Proteolisis , Ratas , Fijación del Tejido
9.
Nat Genet ; 21(1 Suppl): 38-41, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9915499

RESUMEN

Gene expression microarrays hold great promise for studies of human disease states. There are significant technical issues specific to utilizing clinical tissue samples which have yet to be rigorously addressed and completely overcome. Precise, quantitative measurement of gene expression profiles from specific cell populations is at hand, offering the scientific community the first comprehensive view of the in vivo molecular anatomy of normal cells and their diseased counterparts. Here, we propose a model for integrating-in three dimensions-expression data obtained using the microarray.


Asunto(s)
Expresión Génica , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Bases de Datos Factuales , Genoma Humano , Humanos , Masculino , Próstata/anatomía & histología , Próstata/química , Próstata/patología , ARN Mensajero/análisis , ARN Mensajero/genética , ARN Neoplásico/análisis , ARN Neoplásico/genética , Manejo de Especímenes
10.
Nat Genet ; 16(4): 375-8, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9241276

RESUMEN

Primary hyperparathyroidism is a common disorder with an annual incidence of approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal, suggesting that one important step in tumour development is a mutation in a progenitor cell. Approximately 30% of sporadic parathyroid tumours show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 33 tumours we found somatic MEN1 gene mutation in 7, while the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome.


Asunto(s)
Neoplasia Endocrina Múltiple Tipo 1/genética , Mutación , Proteínas de Neoplasias/genética , Neoplasias de las Paratiroides/genética , Proteínas Proto-Oncogénicas , Cromosomas Humanos Par 11 , Dermatoglifia del ADN , Análisis Mutacional de ADN , ADN de Neoplasias/análisis , Eliminación de Gen , Heterocigoto , Humanos
11.
Pathologe ; 34(4): 329-34, 2013 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-23179209

RESUMEN

BACKGROUND: The detection of characteristic genomic aberrations by fluorescence in situ hybridization (FISH) has a high diagnostic impact on lymphomas according to the World Health Organization (WHO). To investigate the reproducibility of non-isotopic ISH results a multicenter trial was carried out involving eight institutes for hematopathology. MATERIAL AND METHODS: Analyses were performed on two diffuse large B-cell lymphomas (DLBCL) without known aberrations, on one follicular lymphoma with a IGH/BCL2 translocation and BCL6 split and on two B-cell lymphomas intermediate between DLBCL and Burkitt's lymphoma with c-MYC and BCL2 rearrangements, one with an additional BCL6 split. Break-apart probes for BCL6 and c-MYC, as well as fusion probes for the c-MYC/IGH and the IGH/BCL2 translocations were used. RESULTS: All aberrations were correctly detected by all centres and no false positive or false negative results were obtained. The numbers of positive cells varied from 25% to 94%. Pearson's correlation coefficient between the centres was always > 0.8. CONCLUSIONS: The ISH analysis of recurrent genomic aberrations in formalin-fixed paraffin-embedded (FFPE) tissue is a highly reproducible technique which yields substantial additive help for lymphoma diagnostics.


Asunto(s)
Aberraciones Cromosómicas , Hibridación in Situ/métodos , Linfoma no Hodgkin/genética , Biomarcadores de Tumor/genética , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/genética , Linfoma de Burkitt/patología , Proteínas de Unión al ADN/genética , Diagnóstico Diferencial , Genes myc/genética , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Hibridación Fluorescente in Situ/métodos , Linfoma Folicular/diagnóstico , Linfoma Folicular/genética , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/patología , Proteínas Proto-Oncogénicas c-bcl-6 , Garantía de la Calidad de Atención de Salud , Reproducibilidad de los Resultados , Translocación Genética/genética
12.
Mol Biol Evol ; 28(3): 1141-55, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21059793

RESUMEN

Sensing the environment and responding appropriately to it are key capabilities for the survival of an organism. All extant organisms must have evolved suitable sensors, signaling systems, and response mechanisms allowing them to survive under the conditions they are likely to encounter. Here, we investigate in detail the evolutionary history of one such system: The phage shock protein (Psp) stress response system is an important part of the stress response machinery in many bacteria, including Escherichia coli K12. Here, we use a systematic analysis of the genes that make up and regulate the Psp system in E. coli in order to elucidate the evolutionary history of the system. We compare gene sharing, sequence evolution, and conservation of protein-coding as well as noncoding DNA sequences and link these to comparative analyses of genome/operon organization across 698 bacterial genomes. Finally, we evaluate experimentally the biological advantage/disadvantage of a simplified version of the Psp system under different oxygen-related environments. Our results suggest that the Psp system evolved around a core response mechanism by gradually co-opting genes into the system to provide more nuanced sensory, signaling, and effector functionalities. We find that recruitment of new genes into the response machinery is closely linked to incorporation of these genes into a psp operon as is seen in E. coli, which contains the bulk of genes involved in the response. The organization of this operon allows for surprising levels of additional transcriptional control and flexibility. The results discussed here suggest that the components of such signaling systems will only be evolutionarily conserved if the overall functionality of the system can be maintained.


Asunto(s)
Escherichia coli K12/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Evolución Molecular , Transactivadores/genética , Transactivadores/metabolismo , Secuencia de Bases , Escherichia coli K12/metabolismo , Proteínas de Escherichia coli/clasificación , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión Génica , Estudios de Asociación Genética , Genoma Bacteriano , Inestabilidad Genómica/fisiología , Genómica , Operón , Filogenia , Estrés Fisiológico/fisiología , Transactivadores/clasificación , Transcripción Genética
13.
Ann Oncol ; 22(11): 2417-2423, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21402619

RESUMEN

BACKGROUND: CALYPSO (CAeLYx in Platinum Sensitive Ovarian) patients compared carboplatin-pegylated liposomal doxorubicin (C-PLD) with carboplatin-paclitaxel (C-P) in patients with late-relapsing recurrent ovarian cancer (ROC). We analyzed outcomes in patients ≥70 years. PATIENTS AND METHODS: Nine hundred and seventy-six patients with taxane-pretreated ROC relapsing >6 months after first- or second-line platinum-based therapy were randomly assigned to 4-weekly C area under the curve (AUC) 5 plus PLD 30 mg/m(2) or 3-weekly C AUC 5 plus P 175 mg/m(2) for six or more cycles. RESULTS: One hundred and fifty-seven (16%) patients ≥70 years (median: 74 years, C-PLD; 73 years, C-P; range 70-82 years) were included (n = 71, C-PLD; n = 86, C-P). In comparing elderly and younger, elderly patients experienced fewer grade ≥2 allergic reactions (P = 0.005) but more grade ≥2 sensory neuropathy (P = 0.007). Myelosuppression did not differ with age. Elderly patients completed planned treatment as frequently as younger (79%, C-PLD; 82%, C-P). In comparing arms within elderly patients, C-P was associated with more grade ≥2 alopecia, sensory neuropathy, arthralgia/myalgia (P < 0.001 for all), severe leukopenia plus febrile neutropenia; C-PLD was associated with more grade ≥2 hand-foot syndrome (P = 0.005). Median progression-free survival was 11.6 months (C-PLD) and 10.3 months (C-P; P = 0.44). CONCLUSIONS: Patients ≥70 years experienced more neuropathy, with a higher incidence in the C-P arm. Similar to all study patients, C-PLD provided a better therapeutic index with less toxicity than C-P in elderly women with platinum-sensitive ROC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/análogos & derivados , Femenino , Humanos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Calidad de Vida , Resultado del Tratamiento
14.
Anaesthesist ; 60(2): 118-24, 2011 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-21060981

RESUMEN

BACKGROUND: The goal of the present study was to evaluate the publication rate of abstracts presented during the German Anesthesia Congress (Deutscher Anästhesiecongress, DAC) and the meeting of the European Society of Anesthesiologists (ESA) in the years 2000 and 2005 in Medline listed journals (http://www.ncbi.nlm.nih.gov/pubmed). In addition, the respective impact factors of the journals in which the articles were published were evaluated (http://www.isiknowledge.com). METHODS: All abstracts of free papers and posters presented at the DAC and ESA from the years 2000 and 2005 were included into the study. The presence of authors and the topics of abstracts in the literature were analyzed by a Medline based inquiry over a time period of 5 years. The search was based on the last name and initials of authors and when these could not be identified in Medline the search was extended by keywords of relevant topics of the abstract. Umlauts "ä/ö/ü" were replaced by "ae/oe/ue" and "ß" was replaced by "ss". Only original papers were included in this analysis. Once an original paper was found the impact factor of the journal in that year was identified. RESULTS: A total of 465 abstracts from the DAC 2000, 378 abstracts from the DAC 2005, 644 abstracts from the ESA 2000 and 720 abstracts from the ESA 2005 were included. Of the abstracts from the DAC 2000, 183 (39%) were published in Medline listed journals, 179 (47%) from DAC 2005, 218 (34%) from ESA 2000 and 233 (32%) from ESA 2005. The ESA abstracts were published in English more often than the DAC abstracts (ESA 2000: 95%; ESA 2005: 95%; DAC 2000: 78%; DAC 2005: 86%). While the publication rate after the ESA remained nearly unchanged between 2000 and 2005, the publication rate after the DAC increased by about 7%. The average impact factors of the publications were 1.777 (DAC 2000), 2.836 (DAC 2005), 1.825 (ESA 2000) and 2.36 (ESA 2005). Independent of the congress (DAC or ESA) where the abstract was presented, most articles were published in the journal Anesthesia & Analgesia. CONCLUSION: In the year 2005 more abstracts of the DAC were published in Medline listed papers than in 2000. When comparing the number of abstracts published in Medline listed journals, more abstracts of the DAC were published compared to abstracts of the ESA. The increase in papers written in English after abstract presentation on the DAC is mostly due to the wider readership which can be reached with manuscripts in the English language. Besides a larger readership, English journals often also have a higher ranked impact factor. This analysis does not claim to be a complete registration of all published abstracts due to the limitation on Medline listed journals and publications in other journals were not rated. Medline was selected because of the widespread and international use of this database.


Asunto(s)
Anestesiología/estadística & datos numéricos , Congresos como Asunto , Publicaciones Periódicas como Asunto , Publicaciones/estadística & datos numéricos , Europa (Continente) , Alemania , Factor de Impacto de la Revista , MEDLINE , Proyectos de Investigación
15.
Nat Commun ; 11(1): 5070, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-33033260

RESUMEN

The evolutionary progression from primary to metastatic prostate cancer is largely uncharted, and the implications for liquid biopsy are unexplored. We infer detailed reconstructions of tumor phylogenies in ten prostate cancer patients with fatal disease, and investigate them in conjunction with histopathology and tumor DNA extracted from blood and cerebrospinal fluid. Substantial evolution occurs within the prostate, resulting in branching into multiple spatially intermixed lineages. One dominant lineage emerges that initiates and drives systemic metastasis, where polyclonal seeding between sites is common. Routes to metastasis differ between patients, and likely genetic drivers of metastasis distinguish the metastatic lineage from the lineage that remains confined to the prostate within each patient. Body fluids capture features of the dominant lineage, and subclonal expansions that occur in the metastatic phase are non-uniformly represented. Cerebrospinal fluid analysis reveals lineages not detected in blood-borne DNA, suggesting possible clinical utility.


Asunto(s)
Linaje de la Célula , Biopsia Líquida , Neoplasias de la Próstata/patología , Líquidos Corporales/metabolismo , Cromosomas Humanos Par 8/genética , Células Clonales , Variaciones en el Número de Copia de ADN/genética , ADN de Neoplasias/genética , Sitios Genéticos , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Filogenia
16.
Science ; 274(5289): 998-1001, 1996 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-8875945

RESUMEN

Laser capture microdissection (LCM) under direct microscopic visualization permits rapid one-step procurement of selected human cell populations from a section of complex, heterogeneous tissue. In this technique, a transparent thermoplastic film (ethylene vinyl acetate polymer) is applied to the surface of the tissue section on a standard glass histopathology slide; a carbon dioxide laser pulse then specifically activates the film above the cells of interest. Strong focal adhesion allows selective procurement of the targeted cells. Multiple examples of LCM transfer and tissue analysis, including polymerase chain reaction amplification of DNA and RNA, and enzyme recovery from transferred tissue are demonstrated.


Asunto(s)
Separación Celular/métodos , Técnicas Histológicas , Rayos Láser , ADN/análisis , Disección , Secciones por Congelación , Humanos , Adhesión en Parafina , Reacción en Cadena de la Polimerasa , Polivinilos , Lesiones Precancerosas/patología , ARN/análisis , Fijación del Tejido
17.
Science ; 276(5311): 404-7, 1997 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-9103196

RESUMEN

Multiple endocrine neoplasia-type 1 (MEN1) is an autosomal dominant familial cancer syndrome characterized by tumors in parathyroids, enteropancreatic endocrine tissues, and the anterior pituitary. DNA sequencing from a previously identified minimal interval on chromosome 11q13 identified several candidate genes, one of which contained 12 different frameshift, nonsense, missense, and in-frame deletion mutations in 14 probands from 15 families. The MEN1 gene contains 10 exons and encodes a ubiquitously expressed 2.8-kilobase transcript. The predicted 610-amino acid protein product, termed menin, exhibits no apparent similarities to any previously known proteins. The identification of MEN1 will enable improved understanding of the mechanism of endocrine tumorigenesis and should facilitate early diagnosis.


Asunto(s)
Clonación Molecular , Genes Supresores de Tumor , Neoplasia Endocrina Múltiple Tipo 1/genética , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogénicas , Secuencia de Aminoácidos , Mapeo Cromosómico , Cromosomas Humanos Par 11 , ADN Complementario/genética , Exones , Mutación del Sistema de Lectura , Humanos , Datos de Secuencia Molecular , Mutación , Proteínas de Neoplasias/química
18.
J Dent Res ; 98(9): 975-984, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31329044

RESUMEN

Understanding of the oral microbiome in relation to periodontal disease in older adults is limited. The composition and diversity of the subgingival microflora and their oligotypes in health and levels of periodontal disease were investigated in this study on older postmenopausal women. The 16S rRNA gene was sequenced using the Illumina MiSeq platform in 1,206 women aged 53 to 81 y. Presence and severity of periodontal disease were defined by Centers for Disease Control and Prevention/American Academy of Periodontology criteria. Composition of the microbiome was determined by 16S rRNA amplicon sequencing and the abundance of taxa described by the centered log2-ratio (CLR) transformed operational taxonomic unit (OTU) values. Differences according to periodontal disease status were determined by analysis of variance with Bonferroni correction. Bacteria oligotypes associated with periodontal disease and health were determined by minimum entropy decomposition and their functions estimated in silico using PICRUSt. Prevalence of none/mild, moderate, and severe periodontal disease was 25.1%, 58.3%, and 16.6%, respectively. Alpha diversity of the microbiome differed significantly across the 3 periodontal disease categories. ß-Diversity differed between no/mild and severe periodontal disease, although considerable overlap was noted. Of the 267 bacterial species identified at ≥0.02% abundance, 56 (20.9%) differed significantly in abundance according to periodontal disease status. Significant linear correlations for pocket depth and clinical attachment level with bacterial amounts were observed for several taxa. Of the taxa differing in abundance according to periodontal disease status, 53% had multiple oligotypes appearing to differ between none/mild and severe periodontal disease. Among older women, taxonomic differences in subgingival microbiome composition and diversity were observed in relation to clinical periodontal disease measures. Potential differences in bacterial subspecies (oligotypes) and their function were also identified in periodontal disease compared with health.


Asunto(s)
Encía/microbiología , Microbiota , Periodontitis/microbiología , Anciano , Anciano de 80 o más Años , Bacterias , Femenino , Humanos , Persona de Mediana Edad , ARN Ribosómico 16S/genética
19.
Br J Cancer ; 99(3): 491-501, 2008 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-18648369

RESUMEN

In the quest for markers of expression and progression for prostate cancer (PCa), the majority of studies have focussed on molecular data exclusively from primary tumours. Although expression in metastases is inferred, a lack of correlation with secondary tumours potentially limits their applicability diagnostically and therapeutically. Molecular targets were identified by examining expression profiles of prostate cell lines using cDNA microarrays. Those genes identified were verified on PCa cell lines and tumour samples from both primary and secondary tumours using real-time RT-PCR, western blotting and immunohistochemistry. Claudin-4, coding for an integral membrane cell-junction protein, was the most significantly (P<0.00001) upregulated marker in both primary and metastatic tumour specimens compared with benign prostatic hyperplasia at both RNA and protein levels. In primary tumours, claudin-4 was more highly expressed in lower grade (Gleason 6) lesions than in higher grade (Gleason >or=7) cancers. Expression was prominent throughout metastases from a variety of secondary sites in fresh-frozen and formalin-fixed specimens from both androgen-intact and androgen-suppressed patients. As a result of its prominent expression in both primary and secondary PCas, together with its established role as a receptor for Clostridium perfringens enterotoxin, claudin-4 may be useful as a potential marker and therapeutic target for PCa metastases.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Proteínas de la Membrana/metabolismo , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/secundario , Secuencia de Bases , Biomarcadores de Tumor/genética , Western Blotting , Línea Celular Tumoral , Claudina-4 , Cartilla de ADN , Humanos , Inmunohistoquímica , Masculino , Proteínas de la Membrana/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias de la Próstata/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
20.
J Appl Microbiol ; 105(3): 706-14, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18399977

RESUMEN

AIM: To investigate the effect of native, heated and glycated bovine serum albumin (BSA) on the ulcerative colitis (UC) and non-UC colonic microbiota in vitro. METHODS AND RESULTS: Continuous flow culture (CFC) models of the human colonic microbiota inoculated with faeces from UC and non-UC volunteers were maintained on BSA as growth substrate. Changes in bacterial populations and short-chain fatty acids were determined. UC and non-UC microbiota differed significantly in microbial populations, with elevated numbers of sulfate-reducing bacteria (SRB) and clostridia in the microbiota from UC patients. Compared with native BSA, glycated BSA modulated the gut microbiota of UC patients in vitro towards a more detrimental community structure with significant increases in putatively harmful bacteria (clostridia, bacteroides and SRB; P < 0.009) and decreases in dominant and putatively beneficial bacterial groups (eubacteria and bifidobacteria; P < 0.0004). The levels of beneficial short-chain fatty acids were significantly decreased by heated or glycated BSA, but were increased significantly by native BSA. CONCLUSION: The UC colonic microbiota maintained in CFC was significantly modified by glycated BSA. SIGNIFICANCE AND IMPACT OF THE STUDY: Results suggest that dietary glycated protein may impact upon the composition and activity of the colonic microbiota, an important environmental variable in UC.


Asunto(s)
Bacterias/efectos de los fármacos , Colitis Ulcerosa/microbiología , Colon/microbiología , Proteínas en la Dieta/farmacología , Alimentos , Albúmina Sérica/farmacología , Adulto , Anciano , Análisis de Varianza , Animales , Bacterias/metabolismo , Técnicas Bacteriológicas , Bacteroides/efectos de los fármacos , Bacteroides/fisiología , Estudios de Casos y Controles , Bovinos , Clostridium/efectos de los fármacos , Clostridium/fisiología , Recuento de Colonia Microbiana/métodos , Digestión , Ácidos Grasos Volátiles/metabolismo , Heces/microbiología , Femenino , Productos Finales de Glicación Avanzada , Calor , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Ribotipificación , Albúmina Sérica Bovina/farmacología , Sulfatos/metabolismo , Albúmina Sérica Glicada
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