RESUMEN
GOALS OF WORK: No blood marker available to date is useful for distinguishing infection-related from neoplasm-related fever. We evaluated the expression of the peripheral blood phagocyte CD11b/CD18 adhesion molecule complex for this purpose. MATERIALS AND METHODS: Neutrophil and monocyte CD11b/CD18 expression was assessed in two cohorts of patients with advanced solid cancer (n = 120) and in healthy controls (n = 63). The cancer series included 89 patients with verified infection, 23 without infection, and eight with neoplastic fever. CD11b/CD18 expression was measured using flow cytometry, and serum C-reactive protein (CRP) concentration was determined with immunoturbidimetric assay. RESULTS: Cancer patients with infection had higher blood neutrophil and monocyte CD11b/CD18 expression levels than patients with neoplastic fever, those with advanced cancer without infection, or healthy controls (p < 0.01 for all analyses). High CD11b/CD18 values were measured exclusively in individuals diagnosed with infection. Receiver-operating characteristic area under the curve (AUC) for neutrophil and monocyte CD11b/CD18 expression for the discrimination of infection from neoplastic fever was 0.80 (95% CI, 0.70 to 0.88), which was superior (p = 0.039 and p = 0.049, respectively) to serum CRP on admission (AUC 0.51, 0.40 to 0.62). CONCLUSIONS: Peripheral blood phagocytic cell CD11b/CD18 expression is useful for making a differential diagnosis between infection and neoplasm-related fever in cancer patients.
Asunto(s)
Antígeno CD11b/metabolismo , Antígenos CD18/metabolismo , Infecciones/diagnóstico , Neoplasias/complicaciones , Adulto , Anciano , Estudios de Casos y Controles , Adhesión Celular , Femenino , Citometría de Flujo , Humanos , Infecciones/complicaciones , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Neutrófilos/metabolismo , Valor Predictivo de las Pruebas , Curva ROC , Regulación hacia ArribaRESUMEN
This article summarizes the current status of 1H MRS in detecting and quantifying a boron neutron capture therapy (BNCT) boron carrier, L-p-boronophenylalanine-fructose (BPA-F) in vivo in the Finnish BNCT project. The applicability of 1H MRS to detect BPA-F is evaluated and discussed in a typical situation with a blood containing resection cavity within the gross tumour volume (GTV). 1H MRS is not an ideal method to study BPA concentration in GTV with blood in recent resection cavity. For an optimal identification of BPA signals in the in vivo 1H MR spectrum, both pre- and post-infusion 1H MRS should be performed. The post-infusion spectroscopy studies should be scheduled either prior to or, less optimally, immediately after the BNCT. The pre-BNCT MRS is necessary in order to utilise the MRS results in the actual dose planning.
Asunto(s)
Compuestos de Boro/sangre , Terapia por Captura de Neutrón de Boro , Fructosa/análogos & derivados , Espectroscopía de Resonancia Magnética/métodos , Adulto , Anciano , Boro/uso terapéutico , Compuestos de Boro/análisis , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Carcinoma/patología , Carcinoma/radioterapia , Femenino , Finlandia , Fructosa/análisis , Fructosa/sangre , Glioblastoma/patología , Glioblastoma/radioterapia , Humanos , Hidrógeno , Isótopos/uso terapéutico , Masculino , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/radioterapia , Fantasmas de Imagen , Plasma , Radiofármacos/uso terapéuticoRESUMEN
Improvements have been made at the FiR 1 BNCT facility to ease the positioning of the patient with a tumor in the head and neck region into a lateral neutron beam. Shoulder recesses were constructed horizontally on both sides of the beam aperture. When shoulder recesses are not needed, they are filled with neutron attenuating filling blocks. MCNP simulations using an anthropomorphic human model BOMAB phantom showed that the main contribution to the increase in the effective dose to the patient's body due to the shoulder recesses was from the neutron dose of the arm. In a position when one arm is inside the shoulder recess, the maximal effective dose of the patient was estimated to be 0.7Sv/h. Dose measurements using the twin ionization chamber technique showed that the neutron dose increased on the sides as predicted by the MCNP model but there was no noticeable change in the gamma doses. When making the recesses into the lithium containing neutron shield material tritium contamination was confined using an underpressurized glove box and machine tools with local exhaust. The shoulder recesses give space for more flexible patient positioning and can be considered as a significant improvement of the Finnish BNCT facility.
Asunto(s)
Terapia por Captura de Neutrón de Boro/instrumentación , Diseño de Equipo , Finlandia , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Fantasmas de Imagen , Postura , Planificación de la Radioterapia Asistida por Computador/instrumentaciónRESUMEN
PACAP is a conserved neuropeptide present in all vertebrates. In the mouse, the PACAP gene and various mRNAs have been isolated. To further characterize the mouse PACAP gene (Adcyap1), we have confirmed its sequence, identified its chromosomal location on distal chromosome 17 and used RT-PCR and 5'RACE in various tissues to identify eight PACAP mRNAs, four of which are novel. Three of these novel transcripts have alternate 5'UTRs, whereas the fourth is altered within the coding region. This is the first report of alternate splicing within the coding region of the PACAP gene. The expression pattern of PACAP in the mouse during embryonic development and adulthood is known. Here, expression of PACAP in the mouse at four postnatal stages in 12 tissues is assessed. We identify continuous expression of PACAP in the brain and eye and stage-specific expression in the gonads and thymus. The complex splicing of PACAP transcripts may regulate the tissue-and stage-specific expression.
Asunto(s)
Empalme Alternativo , Ratones/genética , Neuropéptidos/genética , Regiones no Traducidas 5' , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Linfocitos T CD4-Positivos/metabolismo , Mapeo Cromosómico , Cruzamientos Genéticos , Desarrollo Embrionario y Fetal/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Genes , Masculino , Ratones/embriología , Ratones/crecimiento & desarrollo , Ratones/metabolismo , Datos de Secuencia Molecular , Muridae/genética , Neuropéptidos/biosíntesis , Especificidad de Órganos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , ARN Mensajero/genética , ARN Mensajero/aislamiento & purificación , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Breast cancer patients with c-erbB-2-positive tumours seem to benefit from anthracycline-based adjuvant chemotherapy. The predictive value of c-erbB-2 for taxane sensitivity is not yet clear. The purpose of this study was to assess whether c-erbB-2 expression is associated with clinical sensitivity to docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). A total of 283 patients with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel with sequential MF in advanced breast cancer. Paraffin-embedded blocks of the primary tumour were available for 131 patients (46%). c-erbB-2 status was determined by immunohistochemistry using a polyclonal antibody to the c-erbB-2 protein. C-erbB-2 expression was scored in a semi-quantitative fashion using a 0 to 3+ scale. Staining scores 2+ or greater were considered positive. Response evaluation was performed according to World Health Organization (WHO) recommendations. Overall 54 (42%) patients had c-erbB-2-positive tumours. There was no association between treatment outcome and c-erbB-2 overexpression. The overall response rates (RR) (n=128) among c-erbB-2-negative and -positive patients were 35 and 44%, respectively (P=0.359). In the MF arm (n=62), the RR was somewhat higher in the c-erbB-2 overexpressors (33% versus 18%, P=0.18). In the docetaxel arm the RRs were very similar, regardless of the c-erbB-2 expression (53% versus 53%). While several studies have suggested a prognostic and putative predictive significance of c-erbB-2 overexpression in early breast cancer, the significance of c-erbB-2 expression as a predictive factor for response to various cytotoxic treatments in advanced breast cancer is still controversial. In this study, c-erbB-2 expression could not predict response to either MF or T. Thus, tumours over-expressing c-erbB-2 are not uniformly more sensitive to taxanes and c-erbB-2 expression cannot yet be applied clinically as a predictive factor for response in advanced breast cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Proteínas de Neoplasias/efectos de los fármacos , Paclitaxel/análogos & derivados , Paclitaxel/uso terapéutico , Receptor ErbB-2/efectos de los fármacos , Taxoides , Adolescente , Adulto , Anciano , Neoplasias de la Mama/metabolismo , Quimioterapia Adyuvante , Docetaxel , Femenino , Fluorouracilo/administración & dosificación , Humanos , Metotrexato/administración & dosificación , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Receptor ErbB-2/metabolismoRESUMEN
Rituximab (IDEC-C2B8, Mabthera, Rituxan), a chimeric monoclonal antibody against the B-cell specific CD20-antigen, has been demonstrated to be effective in the treatment of non-Hodgkin's B-cell lymphoma (B-NHL). Previous in vitro studies have shown that direct complement-dependent cytotoxicity (CDC), ADCC and apoptosis are important in the rituximab-induced killing of lymphoma cells. It is, however, unknown whether rituximab penetrates the blood-brain barrier. Therefore, we studied rituximab levels and complement (C) activation in blood and cerebrospinal fluid (CSF) following intravenous rituximab therapy in a patient with relapsing non-Hodgkin's lymphoma with central nervous system (CNS) involvement. Longitudinal samples from blood and CSF were taken at 13 time-points during the treatment period. The results show that the C cascade becomes activated in blood during the first mAb infusion (C3a-desArg concentration rose from 55 to 138 microg/ml during the first 2 hours). After the first infusion the proportions of lymphocytes positive for the CD19- and CD20-antigens in the peripheral blood were reduced from 41% and 35%, respectively, to a level of 2% (for both). In CSF the rituximab concentration increased after successive infusions, but remained below 0.55 microg/ml (compared to a Cmax of 400 microg/ml in peripheral blood). Although a minor and delayed C activation response was seen in the CSF the treatment did not clear CD20-positive cells away from the CNS. Thus, it appears that an intact blood-brain barrier restricts the entry of rituximab into the CNS. Possible options to circumvent this would be dose escalation or intrathecal rituximab treatment.