RESUMEN
Background: We assessed the non-inferiority of accelerated fractionation (AF) (2.4 Gy/fraction) compared with standard fractionation (SF) (2 Gy/fraction) regarding progression-free survival (PFS) in patients with T1-2N0M0 glottic cancer (GC). Patients and methods: In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20-80, Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. Patients were randomly assigned to receive either SF of 66-70 Gy (33-35 fractions), or AF of 60-64.8 Gy (25-27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%. Results: Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9% (95% confidence interval [CI] 73.4-85.4) for SF and 81.7% (95% CI 75.4-87.0) for AF (difference 1.8%, 91% CI-5.1% to 8.8%; one-sided P = 0.047 > 0.045). The cumulative incidences of local failure at 3 years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms. Conclusion: Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC. Clinical trials registration: UMIN Clinical Trial Registry, number UMIN000000819.
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Glotis/patología , Neoplasias Laríngeas/radioterapia , Radioterapia/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Progresión de la Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse, a model of human crescentic glomerulonephritis (CrGN) and systemic vasculitis, is characterized by the production of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and marked leucocytosis. This study was performed to identify the specific populations of leucocytes associated with CrGN and susceptibility loci for pathogenic leucocytosis. Four hundred and twenty female (C57BL/6 × SCG/Kj) F2 intercross mice were subjected to serial flow cytometry examination of the peripheral blood (PB). Kidney granulocytes and monocytes were examined histopathologically. Linkage analyses were performed with 109 polymorphic microsatellite markers. Correlation studies revealed that increase of the granulocytes, F4/80(+) cells, CD3(+) CD4(-) CD8(-) T cells and dendritic cells (DCs) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F4/80(low) cells were observed in crescent, while F4/80(high) cells were around the Bowman's capsules and in the interstitium. Numbers of F4/80(+) cells in crescents correlated significantly with F4/80(+) cell numbers in PB, but not with numbers of F4/80(+) cells in the interstitium. Genome-wide quantitative trait locus (QTL) mapping revealed three SCG/Kj-derived non-Fasâ QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTLs on chromosome 1 affected DCs, granulocytes and F4/80(+) cells, but QTL on chromosome 17 affected DCs and granulocytes. We found CrGN-associated leucocytes and susceptibility QTLs with their positional candidate genes. F4/80(+) cells in crescents are considered as recruited inflammatory macrophages. The results provide information for leucocytes to be targeted and genetic elements in CrGN and vasculitis.
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Predisposición Genética a la Enfermedad , Glomerulonefritis/genética , Leucocitosis/genética , Monocitos/inmunología , Sitios de Carácter Cuantitativo , Vasculitis Sistémica/genética , Animales , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Antígenos de Diferenciación/metabolismo , Autoantígenos/inmunología , Movimiento Celular/genética , Modelos Animales de Enfermedad , Femenino , Ligamiento Genético , Granulocitos/inmunología , Humanos , Riñón/patología , Ratones , Ratones Endogámicos C57BL , Repeticiones de Microsatélite/genética , Peroxidasa/inmunologíaAsunto(s)
Linfoma Folicular/diagnóstico , Linfoma de Células del Manto/diagnóstico , Neoplasia Residual/diagnóstico , Adulto , Anciano , Secuencia de Bases , Cartilla de ADN , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Linfoma Folicular/patología , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) shows poor prognosis and frequent central nervous system (CNS) relapses under anthracycline-containing chemotherapy. The aim of this study was to determine the prognosis and CNS relapse incidence of CD5+ DLBCL in the rituximab era. PATIENTS AND METHODS: We analyzed 337 patients with CD5+ DLBCL who received chemotherapy with (R-chemotherapy group; n = 184) or without (chemotherapy group; n = 153) rituximab. RESULTS: No significant difference was found in clinical background comparisons between the two groups. In the R-chemotherapy group, 60% of the patients were older than 65 years at diagnosis. Both the complete response rate and overall survival (OS) were significantly better in the R-chemotherapy group (P = 0.0003 and P = 0.002, respectively). Multivariate analysis confirmed that chemotherapy without rituximab was associated with unfavorable OS. However, the probability of CNS relapse did not differ between the two groups (P = 0.89). The CNS relapse was strongly associated with short OS (P < 0.0001). In the R-chemotherapy group, 83% of patients who experienced CNS relapse had parenchymal disease. CONCLUSIONS: Our results indicate that rituximab improves the OS of patients with CD5+ DLBCL but does not decrease the CNS relapse rate. More effective treatments with CNS prophylaxis are needed for CD5+ DLBCL patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Antígenos CD5/metabolismo , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundario , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Prednisona/administración & dosificación , Inducción de Remisión , Estudios Retrospectivos , Rituximab , Tasa de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Clinical significance of delayed-onset neutropenia (DON) after autologous hematopoietic stem-cell transplantation (ASCT) has not been well described. We conducted a retrospective cohort study to examine risk factors and clinical impact of DON. DESIGN AND METHODS: Subjects were consecutive 108 patients with B-cell lymphoma receiving ASCT. We defined DON as absolute neutrophil counts <1.0 x 10(9)/l at any point from 30 days onward after ASCT without apparent causes of neutropenia. Documented infectious events were reviewed from 1 to 18 months after ASCT. RESULTS: Fifty-two percent of patients received rituximab. Cumulative incidence of DON was 50% at 1 year. Rituximab usage was identified as an independent risk factor of DON. A total of 117 infectious events were documented, of which 24 events occurred during DON period. Cumulative incidence of total infectious events was 75% and 42% in the groups with and without DON, respectively (P = 0.001). Varicella-zoster virus (P = 0.033) and upper respiratory infection (P = 0.016) were frequent in the patients experiencing DON. In a multivariable analysis, DON remained a significant factor for total infectious events and upper respiratory infection. CONCLUSIONS: Rituximab usage is an independent risk factor of DON. DON correlates with increased occurrence of infectious events. Careful follow-up would be needed after the onset of DON.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Infecciones/complicaciones , Linfoma de Células B/cirugía , Neutropenia/complicaciones , Adolescente , Adulto , Anciano , Femenino , Humanos , Incidencia , Linfoma de Células B/complicaciones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Information on the clinical behavior of the recently proposed primary duodenal follicular lymphoma (DFL) is limited. PATIENTS AND METHODS: Demographic data, signs, symptoms, disease stage, and treatment of the patients diagnosed in National Cancer Center Hospital from 1999 to 2007 were collected and analyzed. RESULTS: Twenty-seven patients were studied. Nineteen patients were asymptomatic at the time of diagnosis. Twenty patients had stage I disease. The histological grade was 1 or 2 in 26 patients. IgH/BCL2 fusion was shown in 20 of the examined 24 cases (83%). Fourteen patients received therapy upon diagnosis (local radiotherapy in 2 patients and chemotherapy in 12 including rituximab therapy), their response rate was 85%, and the estimated progression-free survival (PFS) rate at 3 years was 70%. One patient developed histological transformation. The other 13 patients were followed up; their estimated PFS rate at 3 years was 74%. Five among six cases responded to treatment even after progressive disease. All 27 patients have survived with a median follow-up time of 47.9 months. CONCLUSIONS: The majority of primary DFL patients have a localized tumor of low-grade histology and are positive for t(14;18). Watchful waiting might be an alternative approach for its indolent course; however, further studies are warranted.
Asunto(s)
Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 18/genética , Neoplasias Duodenales/genética , Linfoma Folicular/genética , Recurrencia Local de Neoplasia/genética , Translocación Genética/genética , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Análisis Citogenético , Progresión de la Enfermedad , Neoplasias Duodenales/patología , Neoplasias Duodenales/terapia , Femenino , Humanos , Incidencia , Linfoma Folicular/patología , Linfoma Folicular/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Post-translational modification and degradation of proteins by the ubiquitin-proteasome system are key regulatory mechanisms in cellular responses to various stimuli. The NF-kappaB signaling pathway is controlled by the ubiquitin-mediated proteolysis. RelA/p65, which is a main subunit of NF-kappaB, is ubiquitinated for degradation by SOCS-1, but the functional mechanism of its ubiquitination remains poorly understood. In this study we show that phosphorylation of RelA/p65 at Ser276 prevents its degradation by ubiquitin-mediated proteolysis. In contrast, impairment of Ser276 phosphorylation affects constitutive degradation of RelA/p65. Importantly, we identify Pim-1 as a further kinase responsible for the phosphorylation of RelA/p65 at Ser276. Depletion of Pim-1 hinders not only Ser276 phosphorylation but also transactivation of RelA/p65 target genes. We also show that Pim-1 contributes to recruitment of RelA/p65 to kappaB-elements to activate NF-kappaB signalling after TNF-alpha stimulation. In concert with these results, the knockdown of Pim-1 impairs IL-6 production and augments apoptosis by interfering RelA/p65 activation. These findings provide a model in which Pim-1 phosphorylation of RelA/p65 at Ser276 allows defense against ubiquitin-mediated degradation and whereby exerts activation of NF-kappaB signalling.
Asunto(s)
FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Transducción de Señal/fisiología , Factor de Transcripción ReIA/metabolismo , Activación Transcripcional/fisiología , Ubiquitina/metabolismo , Secuencia de Aminoácidos/fisiología , Animales , Apoptosis/fisiología , Células COS , Chlorocebus aethiops , Regulación hacia Abajo/fisiología , Regulación de la Expresión Génica/fisiología , Células HeLa , Humanos , Interleucina-6/metabolismo , Fosforilación/fisiología , Proteínas Proto-Oncogénicas c-pim-1/genética , Interferencia de ARN , Serina/metabolismo , Activación Transcripcional/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
BACKGROUND: Patients with natural killer (NK) cell neoplasms, aggressive NK cell leukemia (ANKL) and extranodal NK cell lymphoma, nasal type (ENKL), have poor outcome. Both diseases show a spectrum and the boundary of them remains unclear. The purpose of this study is to draw a prognostic model of total NK cell neoplasms. PATIENTS AND METHODS: We retrospectively analyzed 172 patients (22 with ANKL and 150 with ENKL). The ENKLs consisted of 123 nasal and 27 extranasal (16 cutaneous, 9 hepatosplenic, 1 intestinal and 1 nodal) lymphomas. RESULTS: Complete remission rate for ENKL was 73% in stage I, but 15% in stage IV, which was consistent with that for ANKL (18%). The prognosis of ENKL was better than that of ANKL (median survival 10 versus 1.9 months, P < 0.0001) but was comparable when restricted to stage IV cases (4.0 months, P = 0.16). Multivariate analysis showed that four factors (non-nasal type, stage, performance status and numbers of extranodal involvement) were significant prognostic factors. Using these four variables, an NK prognostic index was successfully constructed. Four-year overall survival of patients with zero, one, two and three or four adverse factors were 55%, 33%, 15% and 6%, respectively. CONCLUSION: The current prognostic model successfully stratified patients with NK cell neoplasms with different outcomes.
Asunto(s)
Células Asesinas Naturales/patología , Leucemia/diagnóstico , Linfoma Extranodal de Células NK-T/diagnóstico , Neoplasias Nasales/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Terapia Combinada , Femenino , Humanos , Inmunofenotipificación , Leucemia/terapia , Linfoma Extranodal de Células NK-T/terapia , Masculino , Persona de Mediana Edad , Neoplasias Nasales/terapia , Pronóstico , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
AIMS: The Revised European American Lymphoma classification uses the term Hodgkin's-like anaplastic large cell lymphoma (HD-like ALCL) for borderline cases with features of both anaplastic large cell lymphoma (ALCL) and classical Hodgkin's lymphoma (HL). The aim of this study was to clarify the association between cytotoxic molecule (CM) expression and clinical outcome in HD-like ALCL. METHODS AND RESULTS: Subjects were 59 patients with HD-like ALCL, defined by nodal presentation without mediastinal bulky lesions, T- or null-cell phenotype, CD30+ anaplastic lymphoma kinase (ALK)- phenotype and by confluent sheets or nodules of large cells mimicking classic Hodgkin and Reed-Sternberg cells. We evaluated the presenting features and prognosis of subjects on categorization into two defined groups, namely CM (TIA1 and/or granzyme B)-positive (n = 21) and CM-negative (n = 38). The series consisted of 18 women and 41 men ranging from 16 to 88 years of age (median 59 years). The CM+ group had poorer disease-specific survival than the CM- group (P = 0.02) despite the absence of differences in other clinical characteristics. Multivariate analysis confirmed that CM expression was an independent prognostic factor, in contrast to phenotypic categorization (T-cell vs. null-cell group), which had no prognostic impact on disease-specific survival. CONCLUSION: CM expression is predictive of prognosis in HD-like ALCL.
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Granzimas/metabolismo , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/metabolismo , Proteínas de Unión a Poli(A)/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Regulación Neoplásica de la Expresión Génica , Granzimas/genética , Enfermedad de Hodgkin/patología , Humanos , Linfocitos Nulos/patología , Linfoma de Células B Grandes Difuso/genética , Masculino , Persona de Mediana Edad , Fenotipo , Proteínas de Unión a Poli(A)/genética , Valor Predictivo de las Pruebas , Pronóstico , Células de Reed-Sternberg/patología , Análisis de Supervivencia , Antígeno Intracelular 1 de las Células T , Linfocitos T/patologíaRESUMEN
This study investigated the maximum tolerated dose of S-1 based on the frequency of its dose-limiting toxicities (DLT) with concurrent radiotherapy in patients with locally advanced pancreatic cancer. S-1 was administered orally at escalating doses from 50 to 80 mg m(-2) b.i.d. on the day of irradiation during radiotherapy. Radiation therapy was delivered through four fields as a total dose of 50.4 Gy in 28 fractions over 5.5 weeks, and no prophylactic nodal irradiation was given. Twenty-one patients (50 three; 60 five; 70 six; 80 mg m(-2) seven patients) were enrolled in this trial. At a dose of 70 mg m(-2) S-1, two of six patients demonstrated DLT involving grade 3 nausea and vomiting and grade 3 haemorrhagic gastritis, whereas no patients at doses other than 70 mg m(-2) demonstrated any sign of DLT. Among the 21 enrolled patients, four (19.0%) showed a partial response. The median progression-free survival time and median survival time for the patients overall were 8.9 and 11.0 months, respectively. The recommended dose of S-1 therapy with concurrent radiotherapy is 80 mg m(-2) day(-1). A multi-institutional phase II trial of this regimen in patients with locally advanced pancreatic cancer is now underway.
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Carcinoma/tratamiento farmacológico , Carcinoma/radioterapia , Ácido Oxónico/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Tegafur/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/mortalidad , Terapia Combinada/efectos adversos , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Ácido Oxónico/efectos adversos , Neoplasias Pancreáticas/mortalidad , Análisis de Supervivencia , Tegafur/efectos adversos , Resultado del TratamientoRESUMEN
The treatment of small-round-cell tumors (SRCT) in adult patients remains a challenge to clinicians. In the present study, we analyzed the feasibility and efficacy of high-dose chemotherapy (HDCT) followed by autologous peripheral blood stem-cell rescue as a consolidation therapy exclusively for patients with good disease control through a single regimen of induction chemotherapy and local therapy. Twenty-one patients (12 females, median age 22.0 years) were analyzed, including seven cases with rhabdomyosarcoma (RMS) and 14 cases with Ewing's family tumors (EFT). Overall, survival was 46% and failure-free survival (FFS) was 33% at 3 years. Patients with EFT had better FFS than those with RMS, with an estimated 3-year FFS of 50% (P<0.01). There was a single case of possible treatment-related death and two cases of secondary malignancies. This study cannot conclusively determine the beneficial effects of HDCT for improving treatment outcomes in adult SRCTs due to the small number of subjects. However, study findings suggest that a subgroup of patients with EFT may obtain prolonged survival benefits from this therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sarcoma de Células Pequeñas/tratamiento farmacológico , Sarcoma de Células Pequeñas/terapia , Trasplante de Células Madre , Adolescente , Adulto , Transfusión Sanguínea , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/terapia , Terapia Combinada , Femenino , Humanos , Masculino , Rabdomiosarcoma/terapia , Sarcoma de Ewing/terapia , Sarcoma de Células Pequeñas/mortalidad , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/terapia , Tasa de Supervivencia , Trasplante AutólogoRESUMEN
Neoplasms of natural killer (NK)-lineage are rare. Their prognosis is generally poor except for cases of solitary nasal NK-cell lymphoma. The NK-cell Tumor Study Group performed a survey in Japan on patients diagnosed between 1994 and 1998. Of 228 patients selected for analysis, 40 underwent HSCT (15 allografts and 25 autografts). The underlying diseases were myeloid/NK cell precursor acute leukemia (n = 4), blastic NK-cell lymphoma (n = 11), aggressive NK-cell leukemia (n = 3), and nasal-type extranodal NK-cell lymphoma (n = 22). At the time of HSCT, 22 patients were in complete remission (CR), 11 were in relapse, and seven were primary refractory. All patients received myeloablative conditioning regimens including total-body irradiation. Sixteen died of disease progression, and six of treatment-related causes. Overall, 4-year survival was 39% with a median follow-up of 50 months; this was significantly better than that of patients who did not undergo HSCT (21%, P = 0.0003). For patients transplanted in CR, the 4-year overall survival was 68%, which was significantly better than that of patients who went into CR but did not undergo HSCT (P = 0.03). These findings suggest that the HSCT is a promising treatment strategy for NK-cell lineage.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Células Asesinas Naturales/patología , Leucemia/terapia , Linfoma/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Japón , Leucemia/diagnóstico , Leucemia/patología , Linfoma/diagnóstico , Linfoma/patología , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Trasplante Autólogo , Trasplante HomólogoRESUMEN
BACKGROUND: The majority of lymphomas in the ocular adnexa are low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma). Although radiotherapy is the most frequently applied management, cataract and dry eye are problematic complications. PATIENTS AND METHODS: Between 1973 and 2003, the clinical features of 36 patients with ocular adnexal MALT lymphoma with no symptoms who were managed with no initial therapy after biopsy or surgical resection were retrospectively analyzed. RESULTS: The median patient age was 63 years (range 22-84) and all patients had stage I disease, consisting of 31 unilateral cases and five bilateral cases. With a median follow-up of 7.1 years, 25 (69%) did not require treatment. The median time until the initiation of treatment in the remaining 11 patients (31%) was 4.8 years. Six patients (17%) died, and among them only two (6%) died due to progressive lymphoma. Seventeen patients (47%) progressed, but histologic transformation was recognized in only one (3%). The estimated overall survival rates of the 36 patients after 5, 10 and 15 years were 94%, 94% and 71%, respectively. CONCLUSIONS: In selected patients with ocular adnexal MALT lymphoma, no initial therapy might be an acceptable approach, because 70% of patients remained untreated at a median of 8.6 years, and their survival was comparable to that of reports on immediate therapy.
Asunto(s)
Linfoma de Células B de la Zona Marginal/patología , Neoplasias Orbitales/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B de la Zona Marginal/química , Linfoma de Células B de la Zona Marginal/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Orbitales/secundario , Neoplasias Orbitales/cirugía , Pronóstico , Estudios RetrospectivosRESUMEN
Gemcitabine has been reported to be a potent radiosensitiser in human pancreatic cell lines. This study was conducted to evaluate the efficacy and toxicity of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer. In all, 42 patients with pancreatic cancer that was unresectable but confined to the pancreatic region were treated with external-beam radiation (50.4 Gy in 28 fractions over 5.5 weeks) and weekly gemcitabine (250 mg m(-2), 30-min infusion). Maintenance gemcitabine (1000 mg m(-2) weekly x 3 every 4 weeks) was initiated 1 month after the completion of the chemoradiotherapy and continued until disease progression or unacceptable toxicity. Of the 42 patients, 38 (90%) completed the scheduled course of chemoradiotherapy. The major toxicity was leucopenia and anorexia. There was one death attributed to duodenal bleeding and sepsis. The median survival time was 9.5 months and the 1-year survival rate was 28%. The median progression-free survival time was 4.4 months. In 35 patients with documented disease progression at the time of analysis, 34 (97%) showed distant metastasis as the cause of the initial disease progression. The chemoradiotherapy used in this study has a moderate activity against locally advanced pancreatic cancer and an acceptable toxicity profile. Future investigations for treatment with more systemic effects are warranted.
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Desoxicitidina/análogos & derivados , Desoxicitidina/efectos adversos , Desoxicitidina/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Fármacos Sensibilizantes a Radiaciones/efectos adversos , Fármacos Sensibilizantes a Radiaciones/farmacología , Adulto , Anciano , Terapia Combinada , Desoxicitidina/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Resultado del Tratamiento , GemcitabinaAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino , Técnicas de Cultivo de Célula/métodos , División Celular/efectos de los fármacos , Humanos , Linfoma de Células B/complicaciones , Linfoma de Células B/patología , Rituximab , Factores de Tiempo , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
Although high-dose chemotherapy with autologous peripheral blood stem cell transplantation (autoPBSCT) has been shown or confirmed to be an effective treatment for high-risk and relapsed non-Hodgkin's lymphoma (NHL), relapse after autoPBSCT remains a serious problem. In a clinical trial to overcome relapse, we adopted a treatment plan in which PBSCs purified in vitro to CD34+ cells to deplete tumor cells (CD34+ autoPBSCT), total body irradiation (TBI) of 1200 cGy, and melphalan, 180 mg/m2, were used as a preconditioning regimen. Eighteen patients with relapsed or high-risk NHL participated in the study. This study compared the incidence of complications following CD34+ autoPBSCT preconditioned with the TBI regimen (n = 10): the TBI group; CD34+ autoPBSCT with the non-TBI regimen (n = 8): the non-TBI group; and unselected autoPBSCT with the non-TBI regimen (n = 19): the unselected autoPBSCT control group. After day 30 posttransplantation, 6 of 10 patients treated with the TBI regimen developed 11 infectious complications in total, compared with only 1 of 8 patients treated with the non-TBI regimen and 4 of 19 patients given unselected autoPBSCT. Two fatal complications occurred in the TBI group, but none occurred in the other 2 groups. The CD4+ lymphocyte count at 1 month posttransplantation was significantly lower in the TBI group than in the unselected autoPBSCT group. These findings suggest that the addition of TBI to the preconditioning regimen for CD34+ autoPBSCT is associated with an increased incidence of severe infectious complications after transplantation.
Asunto(s)
Antígenos CD34 , Trasplante de Células Madre Hematopoyéticas/métodos , Infecciones/etiología , Linfoma/terapia , Acondicionamiento Pretrasplante/métodos , Irradiación Corporal Total/efectos adversos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada/métodos , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/normas , Humanos , Linfoma/complicaciones , Masculino , Persona de Mediana Edad , Factores de Riesgo , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/normas , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/métodos , Trasplante Autólogo/normas , Resultado del Tratamiento , Irradiación Corporal Total/normasRESUMEN
Escherichia coli O25 strains that produce heat-stable toxin (ST) have been recently isolated in Japan, and epidemiological study of this type of enterotoxigenic E. coli is required. In this study the heterogeneity of 16 ST-producing and non-producing strains of E. coli O25 was investigated. All eight ST-producing strains were shown to have STIb gene, and seven of them had similar profiles of plasmids, ladder-banding of LPS in SDS-polyacrylamide gel electrophoresis, and chromosomal DNA digestions in pulsed-field gel electrophoresis (PFGE). In contrast, ST-non-producing strains were more heterogeneous in all parameters examined. PFGE of the digested chromosomal DNA with several restriction enzymes was proved to be an effective procedure to compare the closely related strains of E. coli O25.
Asunto(s)
Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/metabolismo , Enterotoxinas/metabolismo , Escherichia coli/genética , Southern Blotting , ADN Bacteriano/análisis , Electroforesis en Gel de Campo Pulsado , Electroforesis en Gel de Poliacrilamida , Escherichia coli/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli , Humanos , Japón , Lipopolisacáridos/análisis , Plásmidos/análisisRESUMEN
The purpose of this study was to investigate the toxicity and the efficacy of re-treatment with rituximab, a chimeric mouse human anti-CD20 monoclonal antibody, in relapsed patients with indolent B-cell non-Hodgkin's lymphoma (NHL) who responded to rituximab in the previous phase I or phase II study. Thirteen patients with relapsed B-cell NHL, each of whom was confirmed to have Revised European-American Lymphoma Classification type II, 1-6 histology (indolent B-NHL), enrolled in this re-treatment study. All were re-treated with rituximab at 375 mg/m2 weekly for 4 consecutive weeks. Rituximab re-treatment was well tolerated with no grade 3/4 nonhematological toxicities, similar to that of the initial treatment. No patients developed detectable human anti-chimeric antibody. Partial responses were observed in 5 of 13 patients (38%; 95% confidence interval [CI], 14% to 68%); 6 patients showed stable disease and 2 showed progressive disease. Overall survival rate was 93% at 19 months of median follow-up after rituximab re-treatment. Median progression-free survival (PFS) after the re-treatment was 5.1 months (95% CI, 4.1 to 5.6 months), and the median PFS after the initial treatment was 8.2 months (95%CI, 5.9 to 11.3 months). Although rituximab re-treatment induced prolonged depletion of normal peripheral blood B cells in all patients, no significant decrease in serum immunoglobulin or complement level was observed. In conclusion, rituximab re-treatment was well tolerated, and it may produce a prolonged PFS in some patients with indolent B-cell NHL who showed initial response to rituximab.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Linfoma de Células B/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/toxicidad , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos/administración & dosificación , Antineoplásicos/toxicidad , Linfocitos B/citología , Proteínas del Sistema Complemento/análisis , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunoglobulinas/sangre , Infecciones/etiología , Recuento de Linfocitos , Linfoma de Células B/complicaciones , Masculino , Persona de Mediana Edad , Recurrencia , Rituximab , Linfocitos T/citología , Resultado del TratamientoRESUMEN
Malignant lymphoma of the female genital tract (FGT) is rare. In this study, 5 peripheral T/natural killer (NK)-cell lymphomas (PTCLs) involving the FGT are reported. They include 2 from the uterus and 1 each from ovary, uterus and ovary, and vagina, and were detected between 1996 and 2000. One of the 2 ovarian tumors was bilateral. In all cases, the FGT was the initial site of clinical presentation of disease. Age at presentation ranged from 21 to 52 years (median, 36 years). One case was stage I disease, 2 were stage II, and 2 were stage IV. All 5 tumors were positive for CD3epsilon, and 3 harbored the Epstein-Barr virus, although the detailed immunophenotypic profiles varied. Three were diagnosed as nasal type T/NK-cell lymphoma, 1 as anaplastic large-cell lymphoma (anaplastic lymphoma kinase [ALK]-positive), and 1 as unspecified PTCL of cytotoxic phenotype, according to the forthcoming World Health Organization classification. Four of 5 patients received laparotomy and chemotherapy. Four patients (in stages II and IV) died of disease within 16 months of the initial diagnosis, whereas only 1 patient (in stage I) is alive without disease at 39 months of follow-up. Our experience in this series provided clinically relevant information on diagnosis, treatment, and outcome for extremely rare tumors of the FGT.
Asunto(s)
Neoplasias de los Genitales Femeninos/patología , Células Asesinas Naturales/patología , Linfoma de Células T/diagnóstico , Linfoma de Células T/patología , Adulto , Femenino , Neoplasias de los Genitales Femeninos/diagnóstico , Humanos , Inmunofenotipificación , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Genetic alteration is considered a probable cause of malignant lymphoma. Folate and methionine metabolism play essential roles in DNA synthesis and DNA methylation, and their metabolic pathways might thus affect disease susceptibility. In the present study, 2 polymorphisms were evaluated for a folate metabolic enzyme, methylenetetrahydrofolate reductase (MTHFR), and one was evaluated for methionine synthase (MS). The 2 polymorphisms, MTHFR677 C-->T and MTHFR1298 A-->C, are reported to reduce the enzyme activity, which causes intracellular accumulation of 5,10-methylenetetrahydrofolate and results in a reduced incidence of DNA double-strand breakage. The MS2756 A-->G polymorphism also reduces the enzyme activity and results in the hypomethylation of DNA. To evaluate the association between malignant lymphoma susceptibility and these polymorphisms, hospital-based case-control study was conducted in Aichi Cancer Center. Ninety-eight patients with histologically confirmed lymphoma and 243 control subjects without cancer were evaluated. Unconditional logistic regression analyses revealed a higher susceptibility with the MTHFR677 CC and the MTHFR1298 AA genotypes (odds ratio, 2.26; 95% confidence interval, 1.26-4.02) when those harboring at least one variant allele in either polymorphism of MTHFR were defined as the reference. For the MS polymorphism, the MS2756 GG genotype also showed a higher susceptibility (odds ratio, 3.83; 95% CI, 1.21-12.1) than those with MS2756 AA or AG types. The significance was not altered when these 3 polymorphisms were evaluated in combination, and the results suggest that folate and methionine metabolism play important roles in the occurrence of malignant lymphomas. Further studies to confirm the association and detailed biologic mechanisms are now required.