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1.
Ann Oncol ; 28(7): 1436-1447, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28379322

RESUMEN

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.


Asunto(s)
Antineoplásicos/uso terapéutico , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/tratamiento farmacológico , Tomografía de Emisión de Positrones/normas , Criterios de Evaluación de Respuesta en Tumores Sólidos , Tomografía Computarizada por Rayos X/normas , Antineoplásicos/efectos adversos , Consenso , Medios de Contraste/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Determinación de Punto Final , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral
2.
Bone Marrow Transplant ; 50(4): 493-8, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25621808

RESUMEN

We compared outcomes of adult patients receiving T-cell-depleted (TCD) hematopoietic SCT (HCT) without additional GVHD prophylaxis at Memorial Sloan Kettering Cancer Center (MSKCC, N=52), with those of patients receiving conventional grafts at MD Anderson Cancer Center (MDACC, N=115) for ALL in CR1 or CR2. Patients received myeloablative conditioning. Thirty-nine patients received anti-thymocyte globulin at MSKCC and 29 at MDACC. Cumulative incidence of grades 2-4 acute (P=0.001, 17.3% vs 42.6% at 100 days) and chronic GVHD (P=0.006, 13.5% vs 33.4% at 3 years) were significantly lower in the TCD group. The non-relapse mortality at day 100, 1 and 3 years was 15.4, 25.0 and 35.9% in the TCD group and 9.6, 23.6 and 28.6% in the unmodified group (P=0.368). There was no difference in relapse (P=0.107, 21.3% vs 35.5% at 3 years), OS (P=0.854, 42.6% vs 43.0% at 3 years) or RFS (P=0.653, 42.8% vs 35.9% at 3 years). In an adjusted model, age >50, cytogenetics and CR status were associated with inferior RFS (hazard ratio (HR)=2.16, P=0.003, HR=1.77, P=0.022, HR=2.47, P<0.001), whereas graft type was NS (HR=0.90, P=0.635). OS and RFS rates are similar in patients undergoing TCD or conventional HCT, but TCD effectively reduces the rate of GVHD.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Depleción Linfocítica , Modelos Biológicos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Linfocitos T , Acondicionamiento Pretrasplante , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Tasa de Supervivencia
3.
FEBS Lett ; 484(3): 202-6, 2000 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-11078879

RESUMEN

Human BAP31 was cleaved at both of its two identical caspase cleavage sites in two previously reported models of apoptosis. We show here that only the most carboxy-terminal site is cleaved during apoptosis induced in HeLa cells by tunicamycin, tumor necrosis factor and cycloheximide, or staurosporine. Similar results were obtained in HL-60 cells using Fas/APO-1 antibodies, or cycloheximide. This limited cleavage, which is inhibited by several caspase inhibitors, removes eight amino acids from human BAP31 including the KKXX coat protein I binding motif. Ectopic expression of the resulting cleavage product induces redistribution of mannosidase II from the Golgi and prevents endoplasmic reticulum to Golgi transport of virus glycoproteins.


Asunto(s)
Caspasas/metabolismo , Proteínas de la Membrana , Proteínas/metabolismo , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Sitios de Unión , Cicloheximida/farmacología , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Células HeLa , Humanos , Manosidasas/metabolismo , Ratones , Ratones Endogámicos BALB C , Transporte de Proteínas , Proteínas Recombinantes de Fusión/metabolismo , Estaurosporina/farmacología , Transfección , Factor de Necrosis Tumoral alfa/farmacología , Tunicamicina/farmacología , Receptor fas/inmunología , Receptor fas/fisiología
6.
J Clin Microbiol ; 32(1): 143-7, 1994 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8126170

RESUMEN

Seventy-nine methicillin-resistant Staphylococcus aureus (MRSA) strains, isolated during 1980 to 1990, were classified as MRSA Aggl- (14 strains) and MRSA Aggl+ (65 strains) strains on the basis of test results in slide agglutination assays designed to detect fibrinogen-binding protein (clumping factor) and protein A on the staphylococcal surface. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that lysostaphin digests of MRSA Aggl- strains contained a high-molecular-weight protein which was not detected in digests of MRSA Aggl+ strains. Immunization of rabbits with an MRSA Aggl- strain produced an antiserum which agglutinated all MRSA Aggl- strains and also 64 of 65 MRSA Aggl+ strains. Only 1 of 68 coagulase-negative staphylococci showed agglutination in this assay. The anti-MRSA Aggl- antiserum reacted mainly with a 230-kDa staphylococcal surface protein but also with a 175-kDa protein, probably formed by proteolysis of the former and a few slightly smaller proteins. These could not be immunologically detected in lysostaphin digests of MRSA Aggl+ strains. Purified antibodies reacting with the 230-kDa protein agglutinated all MRSA Aggl- strains, indicating that the protein is located on the surfaces of staphylococci. The results suggest a tentative role for the 230-kDa protein or its fragments as a novel target to develop more efficient rapid identification methods for S. aureus, including MRSA.


Asunto(s)
Proteínas Bacterianas/aislamiento & purificación , Resistencia a la Meticilina , Staphylococcus aureus/clasificación , Pruebas de Aglutinación , Anticuerpos Antibacterianos , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/aislamiento & purificación , Proteínas Bacterianas/inmunología , Tipificación de Bacteriófagos , Lisostafina/farmacología , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación
7.
Virology ; 211(1): 241-50, 1995 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-7645217

RESUMEN

We have studied the interactions of the G1 and G2 membrane glycoproteins of Uukuniemi virus, a bunyavirus, in virus particles and in Triton X-100-solubilized virus. The G1 glycoprotein in intact virus or in Triton solution could be oxidized into a covalent homodimer using Cu2+ ion as a catalyst. Immunoprecipitations of the glycoproteins from Triton-solubilized virus lysates showed that G1 and G2 do not form a stable heterodimeric or heterooligomeric complex. The oligomeric association of G1 and G2 was further analyzed using centrifugation in sucrose gradients in the presence of Triton X-100. The results indicate that G1 exists as a Triton-resistant pH-insensitive homodimer. This is in contrast to the behavior of G2, which exists as a homodimer and partially as a monomer at pH 6.4 or above and is dissociated completely into a monomer at pH 6.0 or below. The threshold for the dimer-monomer shift of G2 is between pH 6.2 and pH 6.0. Electron microscopy studies show that the surface structure of the virus particle undergoes a pH-dependent change. Studies on the kinetics of virus entry suggest that pH below 6.2 is necessary for the penetration of Uukuniemi virus.


Asunto(s)
Virus Uukuniemi/metabolismo , Proteínas del Envoltorio Viral/química , Proteínas del Envoltorio Viral/metabolismo , Animales , Línea Celular , Células Cultivadas , Centrifugación por Gradiente de Densidad , Embrión de Pollo , Cobre/farmacología , Cricetinae , Fibroblastos , Riñón , Sustancias Macromoleculares , Metionina/metabolismo , Microscopía Electrónica , Peso Molecular , Octoxinol , Oxidación-Reducción , Solubilidad , Radioisótopos de Azufre , Virus Uukuniemi/crecimiento & desarrollo , Virus Uukuniemi/ultraestructura , Proteínas del Envoltorio Viral/ultraestructura
8.
J Virol ; 71(2): 1162-72, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8995638

RESUMEN

Previous studies have suggested that Uukuniemi virus, a bunyavirus, matures at the membranes of the Golgi complex. In this study we have employed immunocytochemical techniques to analyze in detail the budding compartment(s) of the virus. Electron microscopy of infected BHK-21 cells showed that virus particles are found in the cisternae throughout the Golgi stack. Within the cisternae, the virus particles were located preferentially in the dilated rims. This would suggest that virus budding may begin at or before the cis Golgi membranes. The virus budding compartment was studied further by immunoelectron microscopy with a pre-Golgi intermediate compartment marker, p58, and a Golgi stack marker protein, mannosidase II (ManII). Virus particles and budding virus were detected in ManII-positive Golgi stack membranes and, interestingly, in both juxtanuclear and peripheral p58-positive elements of the intermediate compartment. In cells incubated at 15 degrees C the nucleocapsid and virus envelope proteins were seen to accumulate in the intermediate compartment. Immunoelectron microscopy demonstrated that at 15 degrees C the nucleocapsid is associated with membranes that show a characteristic distribution and tubulo-vesicular morphology of the pre-Golgi intermediate compartment. These membranes contained virus particles in the lumen. The results indicate that the first site of formation of Uukuniemi virus particles is the pre-Golgi intermediate compartment and that virus budding continues in the Golgi stack. The results raise questions about the intracellular transport pathway of the virus particles, which are 100 to 120 nm in diameter and are therefore too large to be transported in the 60-nm-diameter vesicles postulated to function in the intra-Golgi transport. The distribution of the virus in the Golgi stack may imply that the cisternae themselves have a role in the vectorial transport of virus particles.


Asunto(s)
Infecciones por Bunyaviridae/virología , Aparato de Golgi/virología , Orthobunyavirus , Animales , Línea Celular , Embrión de Pollo , Aparato de Golgi/ultraestructura , Inmunohistoquímica , Microscopía Electrónica
9.
Eur J Biochem ; 236(3): 904-10, 1996 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-8665912

RESUMEN

Certain methicillin-resistant Staphylococcus aureus strains contain a 230-kDa cell-wall protein which is not present on the surface of other staphylococci. The presence of this 230-kDa protein is associated with a negative test result in commercial assays designed to detect fibrinogen-binding proteins and/or protein A on the staphylococcal surface. We have purified and partially characterised the 230-kDa protein from a lysostaphin digest of a non-agglutinating methicillin-resistant S. aureus strain. Partial amino acid sequence data obtained from the purified protein did not reveal any significant similarities to known proteins which indicates that the protein is novel. The 230-kDa protein was very sensitive to proteolysis; soluble plasmin, or plasmin formed on the bacterial-cell surface, rapidly degraded the 230-kDa protein to a 175-kDa form. The finding that the 230-kDa protein bound to lectins allowed its purification by affinity chromatography on immobilised wheat germ agglutinin. Furthermore, the degradation of the 230-kDa protein was associated with an increased adherence of non-agglutinating methicillin-resistant S. aureus cells to solid-phase fibronectin, fibrinogen or IgG.


Asunto(s)
Proteínas Bacterianas/química , Proteínas Bacterianas/aislamiento & purificación , Fibrinolisina/metabolismo , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/aislamiento & purificación , Staphylococcus aureus/metabolismo , Aglutinación , Secuencia de Aminoácidos , Proteínas Bacterianas/metabolismo , Carbohidratos/análisis , Pared Celular/metabolismo , Cromatografía Líquida de Alta Presión , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Lectinas , Glicoproteínas de Membrana/metabolismo , Resistencia a la Meticilina , Datos de Secuencia Molecular , Peso Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/aislamiento & purificación , Homología de Secuencia de Aminoácido , Tripsina/metabolismo
10.
Biochem Cell Biol ; 68(7-8): 1032-6, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-2121168

RESUMEN

The branch specificity of Escherichia coli beta-galactosidase (EC 3.2.1.23) was studied by analyzing the cleavage of the branched hexasaccharide Gal beta 1-4GlcNAc beta 1-3(Gal beta 1-4GlcNAc beta 1-6)[14C(U)]Gal beta 1-4GlcNAc (1). This hexasaccharide was cleaved to pentasaccharides Gal beta 1-4GlcNAc beta 1-3(GlcNAc beta 1-6) [14C(U)]Gal beta 1-4GlcNAc (3) and GlcNAc beta 1-3(Gal-beta 1-4GlcNAc beta 1-6) [14C(U)]Gal beta 1-4GlcNAc (4) without any appreciable branch specificity. Even the further conversions of the pentasaccharides 3 and 4 into the tetrasaccharide GlcNAc beta 1-3(GlcNAc beta 1-6)[14C(U)]Gal beta 1-4GlcNAc seemed to proceed at similar rates, without any appreciable branch specificity. In marked contrast to the hexasaccharide 1, the pentasaccharide Gal beta 1-4GlcNAc beta 1-3(Gal beta 1-4GlcNAc beta 1-6)[14C(U)]Gal (2), missing the reducing end GlcNAc, is known to be cleaved selectively at the 6-branch; this finding was confirmed in the present study. The different behaviour of hexasaccharide 1 and pentasaccharide 2 reflects differences in the reactivity of their 6-branches; the preferred conformations of these closely related molecules may be quite different.


Asunto(s)
Acetilglucosamina/análogos & derivados , Escherichia coli/enzimología , Oligosacáridos/metabolismo , Polisacáridos/metabolismo , beta-Galactosidasa/metabolismo , Secuencia de Carbohidratos , Cinética , Datos de Secuencia Molecular , Especificidad por Sustrato
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