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1.
PLoS One ; 13(1): e0190860, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29304125

RESUMEN

Non-Hodgkin lymphoma (NHL) affects over 400,000 people in the United States; its incidence increases with age. Treatment options are numerous and expanding, yet efficacy is often limited by toxicity, particularly in the elderly. Nearly 70% patients eventually die of the disease. Many patients explore less toxic alternative therapeutics proposed to boost anti-tumor immunity, despite a paucity of rigorous scientific data. Here we evaluate the lymphomacidal and immunomodulatory activities of a protein fraction isolated from fermented wheat germ. Fermented wheat germ extract was produced by fermenting wheat germ with Saccharomyces cerevisiae. A protein fraction was tested for lymphomacidal activity in vitro using NHL cell lines and in vivo using mouse xenografts. Mechanisms of action were explored in vitro by evaluating apoptosis and cell cycle and in vivo by immunophenotyping and measurement of NK cell activity. Potent lymphomacidal activity was observed in a panel of NHL cell lines and mice bearing NHL xenografts. This activity was not dependent on wheat germ agglutinin or benzoquinones. Fermented wheat germ proteins induced apoptosis in NHL cells, and augmented immune effector mechanisms, as measured by NK cell killing activity, degranulation and production of IFNγ. Fermented wheat germ extract can be easily produced and is efficacious in a human lymphoma xenograft model. The protein fraction is quantifiable and more potent, shows direct pro-apoptotic properties, and enhances immune-mediated tumor eradication. The results presented herein support the novel concept that proteins in fermented wheat germ have direct pro-apoptotic activity on lymphoma cells and augment host immune effector mechanisms.


Asunto(s)
Antineoplásicos/farmacología , Células Asesinas Naturales/inmunología , Activación de Linfocitos/efectos de los fármacos , Linfoma no Hodgkin/patología , Extractos Vegetales/farmacología , Triticum/metabolismo , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Femenino , Fermentación , Humanos , Linfoma no Hodgkin/inmunología , Ratones , Ratones Desnudos , Proteínas de Plantas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
2.
Leuk Lymphoma ; 57(5): 1021-32, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27050240

RESUMEN

Blinatumomab is a member of a novel class of T cell-engaging bispecific antibodies, so-called Bispecific T cell Engager (BiTEs). It is directed against the B cell differentiation antigen CD19 and intended for treatment of B cell malignancies. In clinical phase I/II trials, blinatumomab showed remarkable single-agent activity in patients with relapsed and/or refractory (R/R) non-Hodgkin lymphoma and R/R B cell precursor acute lymphoblastic leukemia (B-precursor ALL). Cytokine release syndrome and neurological side effects were dose-limiting. Adverse effects were well manageable and transient in nature. Based on results of an international phase II trial, blinatumomab received FDA approval for the treatment of R/R B-precursor ALL in December 2014. Ongoing and future trials will contribute to further optimization of blinatumomab-based T cell therapy and have to show that integration of blinatumomab in current and innovative treatment protocols improves overall survival and quality of life of patients with B cell malignancies.


Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Animales , Anticuerpos Biespecíficos/economía , Anticuerpos Biespecíficos/farmacología , Antígenos CD19/metabolismo , Antineoplásicos/economía , Antineoplásicos/farmacología , Complejo CD3/metabolismo , Ensayos Clínicos como Asunto , Análisis Costo-Beneficio , Evaluación Preclínica de Medicamentos , Resistencia a Antineoplásicos , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/patología , Terapia Molecular Dirigida , Neoplasias/inmunología , Neoplasias/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Recurrencia , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Resultado del Tratamiento
3.
AIDS ; 24(11): 1765-70, 2010 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-20453630

RESUMEN

OBJECTIVE: To investigate the survival outcomes for non-Hodgkin lymphoma (NHL) in HIV-infected vs. uninfected patients from the same integrated healthcare system, and to identify prognostic factors for HIV-related NHL in the era of combined antiretroviral therapy. DESIGN: A cohort study. METHODS: Incident NHL diagnosed between 1996 and 2005 were identified from members of Kaiser Permanente California Health Plans. Two-year all-cause and lymphoma-specific mortality by HIV status were examined using multivariable Poisson regression. Among HIV-infected patients, prognostic factors of demographics, lymphoma, and HIV-related characteristics for the same outcomes were also examined. RESULTS: A total of 259 HIV-infected and 8230 HIV-uninfected incident NHL patients were evaluated. Fifty-nine percent of HIV-infected patients died within 2 years after NHL diagnosis as compared with 30% of HIV-uninfected patients. HIV status was independently associated with a doubling of 2-year all-cause mortality (relative risk = 2.0, 95% confidence interval 1.7-2.3). This elevated mortality risk for HIV-infected patients was similar for all race groups, lymphoma stages, and histologic subtypes. HIV-infected patients with CD4 cell count below 200 cells/microl, prior AIDS-defining illness, or both were also at increased risk for lymphoma-specific mortality as compared with HIV-uninfected patients. Among HIV-infected NHL patients, significant prognostic factors for overall mortality included prior AIDS-defining illness and Burkitt's subtype. CONCLUSION: HIV-infected patients with NHL in the combined antiretroviral therapy era continue to endure substantially higher mortality compared with HIV-uninfected patients with NHL. Better management and therapeutic approaches to extend survival time for HIV-related NHL are needed.


Asunto(s)
Infecciones por VIH/mortalidad , Linfoma Relacionado con SIDA/mortalidad , Adulto , Anciano , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , California/epidemiología , Quimioterapia Combinada , Métodos Epidemiológicos , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Linfoma Relacionado con SIDA/inmunología , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico
4.
Rev. bras. hematol. hemoter ; 30(1): 36-40, jan.-fev. 2008. graf, tab
Artículo en Portugués | LILACS | ID: lil-485331

RESUMEN

Linfomas não-Hodgkin (LNH) extranodais representam cerca de um terço de todos os linfomas e atualmente apresentam taxa de incidência maior que a de linfomas nodais. Diferenças entre LNH nodais e extranodais incluem etiologia, formas de apresentação e resposta terapêutica, entretanto não dispomos de dados na nossa população. Este estudo teve como objetivo caracterizar os LNH extranodais diagnosticados no Hospital Aristides Maltez, em Salvador-Bahia. Foram avaliados, retrospectivamente, 145 diagnósticos de linfoma não-Hodgkin, segundo a OMS-2001, no período de janeiro de 1999 a julho de 2001. A freqüência de linfomas extranodais foi de 30,3 por cento. A idade média dos pacientes foi de 55,6 anos e a relação homem/mulher foi de 1:1. A maioria dos pacientes apresentava estadios avançados (III ou IV de Ann Arbor), presença de sintomas B, LDH normal, bom desempenho pela escala do ECOG e IPI entre zero e dois. Nove pacientes estão vivos e em remissão completa (22,5 por cento) após um seguimento médio de 23 meses. O sítio extranodal mais comumente acometido foram as tonsilas, seguidas pela cavidade oral, pele e trato gastrointestinal, dentre outros. O linfoma difuso de grandes células B foi o mais comum subtipo histológico, seguido pelo linfoma anaplásico de grandes células. Concluímos que o mais freqüente sítio extranodal de apresentação em nosso estudo difere da maioria da literatura, porém nossa freqüência de linfoma extranodal é semelhante à mesma.


Extranodal non-Hodgkins lymphomas represent approximately one third of all lymphomas and currently have an incidence higher than nodal lymphomas. Differences in etiology, presentation and outcome of these lymphomas have been reported. However, there are no data in our population. This study was carried out in the Pathological Anatomy Service of Aristides Maltez Hospital in Salvador, Bahia. One hundred and forty-five non-Hodgkins lymphomas cases according to the WHO-2001 classification detected between January 1999 and July 2001 were evaluated. The frequency of extranodal lymphomas was 30.3 percent. The mean age of the patients was 55.6 percent years and the male/female ratio was 1:1. The majority of the patients presented with advanced stages, B symptoms, normal LDH, ECOG between o and 2 and IPI between O and 2. Nine patients are still alive in complete remission (22.5 percent) with a mean follow-up of 23 months. The main extranodal sites were the tonsils followed by the oral cavity, skin and gastrointestinal tract. Diffuse large B-Cell lymphoma was the mains histological subtype, followed by anaplastic large-cell lymphoma. In summary, the mains extranodal site in our study was different from the masority of reports. However our extranodal lymphoma frequency was similar.


Asunto(s)
Humanos , Evolución Clínica , Linfoma no Hodgkin , Linfoma no Hodgkin/inmunología
6.
Rev Esp Med Nucl ; 25(1): 42-54, 2006.
Artículo en Español | MEDLINE | ID: mdl-16540013

RESUMEN

Radioimmunotherapy treatment for lymphoma is a novel targeted therapeutic approach. Several years of development of radioimmunotherapeutic compounds came to fruition in February of 2002 when 90Y-ibritumomab tiuxetan (Zevalin, Y2B8) was approved in the USA and later in Europe, for the treatment of relapsed or refractory, low grade or transformed B-cell lymphoma in the USA. 90Y-ibritumomab tiuxetan utilizes a monoclonal anti-CD20 antibody to deliver beta-emitting yttrium-90 to the malignant B-cells. Clinical trials have demonstrated its efficacy, with observed clinical responses in the 80 % range. This product has become available in Europe, with simplified administration, for the treatment of relapsed follicular lymphoma. A similar anti-CD20 radiotherapeutic compound, 131I-tositumomab, was subsequently approved in the USA. Promising studies exploring expanded applications of radioimmunotherapy as consolidation, as part of transplant, or in other histologic types have been recently completed or are under way. Radioimmunotherapy has been shown to be an effective and clinically relevant complementary therapeutic approach for patients with lymphoma, bringing the Nuclear Medicine into lymphoma therapeutics.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Inmunoconjugados/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Linfoma no Hodgkin/radioterapia , Radioinmunoterapia , Radioisótopos de Itrio/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales de Origen Murino , Especificidad de Anticuerpos , Antígenos CD/inmunología , Antígenos CD20/inmunología , Antígenos de Neoplasias/inmunología , Ensayos Clínicos como Asunto , Contraindicaciones , Resistencia a Antineoplásicos , Unión Europea , Predicción , Humanos , Inmunoconjugados/administración & dosificación , Inmunoconjugados/efectos adversos , Radioisótopos de Yodo/administración & dosificación , Radioisótopos de Yodo/efectos adversos , Linfoma de Células B/inmunología , Linfoma de Células B/radioterapia , Linfoma no Hodgkin/inmunología , Selección de Paciente , Radioinmunoterapia/efectos adversos , Radioinmunoterapia/métodos , Rituximab , Terapia Recuperativa , Tetraspaninas , Resultado del Tratamiento , Estados Unidos , Radioisótopos de Itrio/administración & dosificación , Radioisótopos de Itrio/efectos adversos
7.
Curr Hematol Malig Rep ; 1(4): 205-13, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20425315

RESUMEN

Immunotherapy with rituximab (a chimeric anti-CD20 monoclonal antibody), alone or in combination with chemotherapy, has improved the treatment outcome of patients with non-Hodgkin's lymphoma (NHL), but the in vivo mechanisms by which rituximab exerts its effects have not been elucidated. The mechanisms underlying resistance are not known. In addition to the proposed actions mediated by rituximab (such as complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and apoptosis), rituximab may signal the tumor cells and inhibit constitutively activated survival signaling pathways (Raf-1-MEK1/2-ERK1/2, p38 MAPK, NF-kappaB, and Akt), resulting in inhibition of cell growth and of selectively anti-apoptotic gene products such as Bcl-2 and Bcl-(xL). The inhibition of these anti-apoptotic gene products by rituximab sensitizes drug-resistant tumor cells to apoptosis induced by a variety of cytotoxic chemotherapeutic drugs. Also, rituximab sensitizes NHL cells to apoptosis resulting from upregulation of death receptors, implicating a novel in vivo role of host involvement in rituximab-mediated effects. We have developed rituximab-resistant clones that do not respond to rituximab-mediated cell signaling. The clones exhibited hyperactivated cell survival pathways and overexpression of anti-apoptotic gene products and could not be chemosensitized by rituximab. Inhibitors of the survival signaling pathways reverse drug resistance in both wildtype cells and resistant clones. These findings identify several novel intracellular pathways modifyed by rituximab that sensitize NHL cells to both chemotherapy and immunotherapy, as well as several therapeutic targets whose modifications reverse resistance. These findings have clinical relevance for both prognosis and novel treatment strategies for patients with NHL.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Antígenos CD20/fisiología , Transducción de Señal/efectos de los fármacos , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Formación de Anticuerpos/efectos de los fármacos , Antígenos CD20/inmunología , Antineoplásicos/inmunología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral/efectos de los fármacos , Células Clonales/efectos de los fármacos , Citotoxicidad Inmunológica/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inmunoterapia , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , FN-kappa B/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/fisiología , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/fisiología , Rituximab , Factor de Transcripción YY1/antagonistas & inhibidores , Factor de Transcripción YY1/fisiología , Proteína bcl-X/antagonistas & inhibidores , Proteína bcl-X/fisiología
8.
J Immunol ; 175(4): 2174-83, 2005 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-16081784

RESUMEN

Rituximab treatment of B non-Hodgkin's lymphoma (NHL) cell lines inhibits the constitutive NF-kappaB activity and results in the sensitization of tumor cells to both chemotherapy and Fas-induced apoptosis. Cells expressing dominant active IkappaB or treated with NF-kappaB-specific inhibitors were sensitive to both drugs and Fas agonist mAb (CH-11)-induced apoptosis. Down-regulation of Bcl-xL expression via inhibition of NF-kappaB activity correlated with chemosensitivity. The direct role of Bcl-xL in chemoresistance was demonstrated by the use of Bcl-xL-overexpressing Ramos cells, Ramos hemagglutinin (HA)-Bcl-x, which were not sensitized by rituximab to drug-induced apoptosis. However, inhibition of Bcl-xL in Ramos HA-Bcl-x resulted in sensitization to drug-induced apoptosis. The role of Bcl-xL expression in the regulation of Fas resistance was not apparent; Ramos HA-Bcl-x cells were as sensitive as the wild type to CH-11-induced apoptosis. Several lines of evidence support the direct role of the transcription repressor yin-yang 1 (YY1) in the regulation of resistance to CH-11-induced apoptosis. Inhibition of YY1 activity by either rituximab or the NO donor DETANONOate or after transfection with YY1 small interfering RNA resulted in up-regulation of Fas expression and sensitization to CH-11-induced apoptosis. These findings suggest two mechanisms underlying the chemosensitization and immunosensitization of B-NHL cells by rituximab via inhibition of NF-kappaB. The regulation of chemoresistance by NF-kappaB is mediated via Bcl-xL expression, whereas the regulation of Fas resistance by NF-kappaB is mediated via YY1 expression and activity. The potential clinical significance of these findings is discussed.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Linfoma no Hodgkin/inmunología , FN-kappa B/antagonistas & inhibidores , Receptor fas/fisiología , Anticuerpos Monoclonales de Origen Murino , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/inmunología , Resistencia a Antineoplásicos/inmunología , Humanos , Inmunidad Innata , Linfoma no Hodgkin/metabolismo , FN-kappa B/metabolismo , Nitrilos/farmacología , Compuestos Nitrosos/farmacología , Rituximab , Sulfonas/farmacología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/inmunología , Receptor fas/biosíntesis , Receptor fas/inmunología
9.
Clin Lymphoma ; 5 Suppl 1: S22-6, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15498146

RESUMEN

Targeted radioimmunotherapy, including yttrium 90-labeled ibritumomab tiuxetan (Zevalin) and iodine I 131 tositumomab (Bexxar), has the potential to increase the cure rate for patients with CD20+ B-cell malignancies who are undergoing autologous hematopoietic stem cell transplantation. The results of phase I and II trials suggest that radioimmunoconjugates can be safely combined with high-dose chemotherapy, although the optimal approach remains to be established. This review focuses on the use of 90Y ibritumomab tiuxetan combined with high-dose chemotherapy in the setting of autologous hematopoietic stem cell transplantation.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/radioterapia , Trasplante de Células Madre , Radioisótopos de Itrio/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Antígenos CD20 , Ensayos Clínicos como Asunto , Terapia Combinada , Humanos , Linfoma no Hodgkin/inmunología , Radioinmunoterapia/métodos , Trasplante Autólogo , Radioisótopos de Itrio/administración & dosificación
10.
Anticancer Res ; 22(6C): 4187-90, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12553054

RESUMEN

The immunomodulatory and antimetastatic activity of standardized aqueous mistletoe extract (sME) was evaluated in BALB/c-mice. Regular subcutaneous (s.c.) applications (three times per week for 14 consecutive days; 2, 20, 100 and 500 micrograms per injection and mouse) up-regulated thymocyte and peripheral blood leukocyte counts in tumor-bearing mice. Tumor weight and tumor volume were significantly down-regulated after application of sME doses greater than 20 micrograms per injection. To check the influence of sME treatment on growth of experimental metastases, RAW 117 H 10 lymphosarcoma cells and L-1 sarcoma cells were intravenously inoculated into BALB/c-mice to establish liver and lung colonization, respectively. sME was regularly administered starting 24 hours after tumor cell challenge. Organ colonization was investigated on day 14 after tumor cell inoculation and demonstrated statistically significant (p < 0.05) reductions of experimental liver and lung metastases for sME-treated mice.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Linfoma no Hodgkin/tratamiento farmacológico , Preparaciones de Plantas/farmacología , Proteínas de Plantas , Sarcoma Experimental/tratamiento farmacológico , Toxinas Biológicas/farmacología , Animales , División Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/inmunología , Neoplasias Hepáticas Experimentales/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/secundario , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/patología , Ratones , Ratones Endogámicos BALB C , Muérdago/química , Proteínas Inactivadoras de Ribosomas Tipo 2 , Sarcoma Experimental/inmunología , Sarcoma Experimental/patología
11.
BioDrugs ; 15(3): 151-62, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11437681

RESUMEN

Lymphomas are the fifth most common malignancy in the United States and are increasing in incidence. Despite being among the most responsive malignancies to radiation and chemotherapy, the majority of patients relapse or have progressive disease. Monoclonal antibodies (MAbs) directed at cell-specific surface antigens have been useful in the diagnosis of lymphomas and, more recently, the therapeutic mouse-human chimeric MAb rituximab has demonstrated effectiveness in B cell lymphomas. Conjugating MAbs to radionuclides is a strategy for improving the efficacy of MAb lymphoma therapy by delivering radiation in close proximity to the tumour (radioimmunotherapy or RIT). In addition, the low dose rate of the delivered radiation may exert a greater antitumour activity than an equivalent dose of conventional external beam radiation. The antigenic targets for MAb therapy have included CD20, CD22, HLA-DR, and B cell idiotype. Radionuclides that have been used include iodine-131, yttrium-90, and copper-67; there are relative merits and disadvantages to each source of radiation. Clinical studies to date have focused on relapsed and refractory patients with both indolent and aggressive lymphomas, although more recent studies have included previously untreated patients with indolent lymphoma. Radioimmunoconjugate has been delivered as either single or multiple doses. Response rates have varied widely, dependent on the patient population and the response criteria. Of note, complete responses can be achieved in this typically refractory patient group. Toxicities have generally consisted of mild infusion-related nausea, fever, chills, and asthenia. Neutropenia and thrombocytopenia are the dose-limiting toxicities and have prompted the incorporation of autologous stem cell support as a means of achieving dose escalation. To date, RIT has been delivered to highly selected patients in relatively few centres with requisite equipment and specialised personnel. In addition to these requirements, cost is likely to be a barrier to widespread use. The combination of RIT with chemotherapy at conventional or high dose, or with biological agents is a fertile area for investigation. The potential of RIT in the treatment for lymphomas will be defined only by well designed comparative prospective clinical studies.


Asunto(s)
Linfoma no Hodgkin/terapia , Radioinmunoterapia , Animales , Anticuerpos Monoclonales/uso terapéutico , Humanos , Linfoma no Hodgkin/inmunología , Radiofármacos/uso terapéutico
12.
Anticancer Res ; 21(6A): 3981-7, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11911280

RESUMEN

The antitumoral and immunostimulating properties of rViscumin (recombinant mistletoe lectin) were investigated in two mouse tumor models. After intravenous inoculation with RAW-117-P or L-1 sarcoma cells in Balb/c mice, rViscumin was given s.c. at non-toxic doses ranging from 0.3 to 150 ng rViscumin/kg. One set of experiments was performed to investigate the survival of rViscumin-treated animals. Another set was carried out to analyze the effect of rViscumin treatment on the number of tumor colonies in infiltrated lungs (RAW-117P) or liver (L-1) and the activation of immune cell subsets, respectively. An overall prolonged survival time after treatment with rViscumin and a reduction in the number of tumor colonies after administration of certain rViscumin doses was observed. Immunophenotyping of the peripheral leukocytes of treated mice revealed increased numbers of T-lymphocytes, pan-NK cells and activated monocytes. The results indicate that rViscumin has antineoplastic properties and might therefore be a promising candidate in cancer therapy.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Antineoplásicos/farmacología , Preparaciones de Plantas , Proteínas de Plantas , Sarcoma Experimental/tratamiento farmacológico , Toxinas Biológicas/farmacología , Animales , Ensayos de Selección de Medicamentos Antitumorales , Inmunocompetencia , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/inmunología , Neoplasias Hepáticas Experimentales/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/secundario , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Proteínas Recombinantes/farmacología , Proteínas Inactivadoras de Ribosomas Tipo 2 , Sarcoma Experimental/inmunología , Sarcoma Experimental/secundario , Células Tumorales Cultivadas
13.
São Paulo; s.n; 2001. 96 p. ilus, tab, graf.
Tesis en Portugués | LILACS | ID: lil-313763

RESUMEN

Partindo de dois oligonucleotídeos degenerados derivados de uma fração conservada da região pol de retrovírus conhecidos, foi pesquisada a presença de agente viral exógeno ou de uma seqüência endógena similar as retrovirais (ERV). A partir da amplificação do DNA pela técnica de PCR, foram testadas células mononucleares periféricas de 33 portadores de paraparesia crural espática de evolução crônica sem agente etiológico conhecido, produzindo um fragmento de aproximadamente 500 bp em 8 destas amostras...


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Enfermedades de la Médula Espinal/virología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/sangre , Paraparesia Espástica/metabolismo , Paraparesia Espástica/virología , Paraparesia Espástica Tropical/metabolismo , Paraparesia Espástica Tropical/virología , Retroviridae , Western Blotting , Diagnóstico Clínico , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa , Serología , Serodiagnóstico del SIDA/clasificación , Serodiagnóstico del SIDA/métodos , Serodiagnóstico del SIDA , Pruebas Serológicas/métodos , Pruebas Serológicas
14.
Br J Dermatol ; 141(4): 739-46, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10583130

RESUMEN

Paraneoplastic pemphigus (PP) is an autoimmune disease, which is frequently associated with non-Hodgkin's lymphoma. Autoantibodies against components of the cytoplasmic plaque of epithelial desmosomes are usually present in the sera and are believed to play a major pathogenic part in acantholysis and suprabasal epidermal blistering. However, another typical histological feature of PP, interface dermatitis with keratinocyte dyskeratosis, is shared with skin diseases that involve epithelial damage mediated by T cells. Here, we present the detailed characterization of the cutaneous T-cell response in a patient with PP and demonstrate a selective epidermal accumulation of activated CD8+ T cells together with an increased local production of interferon-gamma and tumour necrosis factor-alpha, and a strong expression of HLA-DR and ICAM-1 on keratinocytes. Apoptosis was identified as a key mechanism of keratinocyte death, and appeared independent of the FAS/FAS ligand (FAS-L) pathway, as epidermal expression of FAS was not increased compared with normal skin, and FAS-L was undetectable on the protein and mRNA level. Triple therapy with high-dose corticosteroids, cyclophosphamide and intravenous immunoglobulins reduced levels of pemphigus-like autoantibodies and reversed the cutaneous inflammatory reaction leading to long-standing clinical remission. Our findings support the concept of a major contribution of cytotoxic T lymphocytes to the immunopathology of paraneoplastic pemphigus.


Asunto(s)
Erupciones por Medicamentos/etiología , Inmunosupresores/efectos adversos , Linfoma no Hodgkin/tratamiento farmacológico , Pénfigo/etiología , Vidarabina/análogos & derivados , Adulto , Linfocitos T CD8-positivos/patología , Erupciones por Medicamentos/inmunología , Erupciones por Medicamentos/patología , Epidermis/inmunología , Femenino , Antígenos de Histocompatibilidad Clase II/análisis , Humanos , Inmunohistoquímica , Inmunofenotipificación , Etiquetado Corte-Fin in Situ , Molécula 1 de Adhesión Intercelular/análisis , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/patología , Pénfigo/inmunología , Pénfigo/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Vidarabina/efectos adversos
15.
Lik Sprava ; (3): 125-30, 1998 May.
Artículo en Ruso | MEDLINE | ID: mdl-9695591

RESUMEN

Immunologic parameters were studied in 54 patients with myeloma multiplex (MM), acute leukosis (AL), non-Hodgkin's disease (NHD) before and after in vitro exposure of these patients' blood to weak constant magnetic field (CMF) and CMF in combination with variable magnetic field (VMF). Blood irradiation with CMF over 60 min in AL and MM patients brought about in some cases enhancement of the expression of +CD3, +CD4 and CD8 together with augmentation of the immunoregulatory index. At the same time phagocytic activity of leucocytes got increased as did digesting capability and index of completeness of phagocytosis, i.e. exposure to CMF prevents a blockade of receptors for neutrophilic complement, increases their phagocytic activity and antibody-dependent cellular cytotoxicity. In studying immunocompetent cells of NHD patients' blood, T-helpers were found out to be moderately decreased, with T-suppressors to a greater extent so. Study of CMF and VMF effects on MM and AL patients' blood has shown an immunocorrective action thereof though to a lesser extent so.


Asunto(s)
Antígenos CD/inmunología , Subgrupos de Linfocitos B/inmunología , Leucemia/terapia , Linfoma no Hodgkin/terapia , Magnetismo/uso terapéutico , Mieloma Múltiple/terapia , Subgrupos de Linfocitos T/inmunología , Enfermedad Aguda , Relación CD4-CD8 , Equipos y Suministros , Humanos , Técnicas In Vitro , Leucemia/inmunología , Linfoma no Hodgkin/inmunología , Mieloma Múltiple/inmunología , Fagocitosis
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 17(6): 325-7, 1997 Jun.
Artículo en Chino | MEDLINE | ID: mdl-9863121

RESUMEN

OBJECTIVE: To seek for the effective therapeutical method in treating non-Hodgkin's lymphoma (NHL). METHODS: One hundred and sixty seven patients with non-Hodgkin's lymphoma were randomly divided into two groups, the treatment group, which consisted of 112 cases using Chinese herbs combined with chemotherapy and 55 cases of control group were treated by chemotherapy only. RESULTS: The effective rate (CR + PR) in the combined group was 91.96% and survival rates of 1-, 3- and 5-year were 85.7%, 54.5% and 29.5% respectively, and median survival time was 554 days. In control group the effective rate was 72.73% and 1-, 3- and 5-year survival rates were 76.4%, 38.2% and 18.2% respectively, and the median survival time was 465 days. The difference of effective rates or 3-year survival rates between two groups was significant (P < 0.05). In the combined group the activity of NK cell, OKT3, OKT4 and ratio of OKT4/OKT8 were obviously raised after treatment (P < 0.01). And the level of platelet adhesion rate and the blood viscosity markedly decreased (P < 0.01), but in the control group the values of these indexes did not distinctly change. CONCLUSION: Chinese herbs could enhance the immunologic function and improve the viscosity of blood of the patients with NHL. The side effect in the combination therapy group was less and milder than that in the chemotherapy group. These showed that Chinese herbs combined with chemotherapy was a safe and effective method for treating NHL and deserve to be recommended.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Medicamentos Herbarios Chinos/administración & dosificación , Linfoma no Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Relación CD4-CD8 , Niño , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Hemorreología , Humanos , Células Asesinas Naturales/inmunología , Linfoma no Hodgkin/inmunología , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Estudios Prospectivos , Tasa de Supervivencia , Vincristina/administración & dosificación
18.
Bone Marrow Transplant ; 16(1): 95-101, 1995 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-7581136

RESUMEN

Autologous bone marrow transplantation (ABMT) is used increasingly for the treatment of acute leukemias, lymphomas and solid tumors. Since ABMT is burdened by high risk of relapse, mafosfamide or 4-hydroperoxycyclophosphamide chemical marrow purging is employed. Mafosfamide acts by exerting a potent cytotoxic effect and by promoting apoptosis of leukemic cells. A third proposed mechanism of action involves an effect on immune regeneration in vivo. It was the aim of this study to investigate natural killer (NK) cell regeneration in a group of patients undergoing mafosfamide-purged ABMT. Fifteen patients (8 acute myelogenous leukemia, AML; 4 acute lymphoblastic leukemia, ALL; 3 non-Hodgkin's lymphoma, NHL) were treated with high-dose chemotherapy followed by transplantation with marrow purged with mafosfamide. Prior to ABMT and at different intervals thereafter, NK cell number and function were studied by evaluating the percentage of circulating CD16 positive cells and cytotoxic activity against the leukemic cell line, K562. In comparison to pre-ABMT values, AML patients showed a significant increase in cytotoxic activity, expressed as percentage of chromium release (42.5 +/- 3 vs 32.5 +/- 6, P < or = 0.025 at 4 months) which still persisted at 12 months post-ABMT (54 +/- 6, P < or = 0.05). The behavior of NK functional activity was paralleled by an increase of the percentage of CD16-positive cells (8.4 +/- 2.2 vs 5 +/- 1.3, P < or = 0.05 at 4 months; 12.8 +/- 2.4, P < or = 0.005 at 12 months post-ABMT). Similar significant and long-lasting increments in NK cells were also found in NHL patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Purgación de la Médula Ósea , Trasplante de Médula Ósea/inmunología , Ciclofosfamida/análogos & derivados , Células Asesinas Naturales/inmunología , Leucemia Mieloide Aguda/terapia , Linfoma no Hodgkin/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Recuento de Células , Terapia Combinada , Femenino , Humanos , Células Asesinas Naturales/patología , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/patología , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología
19.
Nutr Cancer ; 11(2): 83-92, 1988.
Artículo en Inglés | MEDLINE | ID: mdl-3362723

RESUMEN

Zinc status and the effect of zinc supplementation were assessed in groups of patients with non-Hodgkin's lymphoma and Hodgkin's disease; patients were either untreated or in remission. In the patients in remission, plasma zinc was normal; and whereas 30% of untreated patients had low plasma zinc, the group as a whole did not differ from normal. For mononuclear cell zinc, the range of values in the disease group was far wider than in controls, but there was no significant difference between the means of the groups. Granulocyte zinc was significantly lower in both the groups of patients in remission from non-Hodgkin's lymphoma and Hodgkin's disease compared with the control group. Significant increases were found in the plasma copper, ceruloplasmin, and the copper-to-zinc ratio in several of the patient groups. Plasma zinc increased by 23% with zinc supplementation (50 mg elemental Zn/day), but there was no effect on mononuclear cell or granulocyte zinc. Apart from granulocyte zinc, there is little evidence of zinc deficiency in non-Hodgkin's lymphoma or Hodgkin's disease. However, the presence of depleted granulocyte zinc levels could modify the immune function of this cell population.


Asunto(s)
Enfermedad de Hodgkin/sangre , Leucocitos/análisis , Linfoma no Hodgkin/sangre , Zinc/sangre , Adulto , Anciano , Femenino , Granulocitos/análisis , Enfermedad de Hodgkin/inmunología , Humanos , Leucocitos Mononucleares/análisis , Linfoma no Hodgkin/inmunología , Masculino , Persona de Mediana Edad , Zinc/uso terapéutico
20.
Cancer ; 54(10): 2294-9, 1984 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-6435855

RESUMEN

The simultaneous occurrence of two different lymphomas in a 57-year-old white woman is reported: mycosis fungoides and a leukemic lymphoplasmacytoid immunocytoma. The first was confirmed by histologic study and electron microscopy, and the latter by histologic study and immunoperoxidase staining. The lymphoid cells in the involved bone marrow and peripheral blood expressed the same surface immunoglobulin as was found in the cytoplasm of the immunocytoma cells, i.e., IgM-lambda. The clonal B-cell expansion was brought into a lasting remission by chlorambucil, but the cutaneous lymphoma proved to be refractory to therapy. The patient died 38 months after diagnosis.


Asunto(s)
Linfoma no Hodgkin/patología , Micosis Fungoide/patología , Neoplasias Primarias Múltiples/inmunología , Neoplasias Cutáneas/patología , Clorambucilo/uso terapéutico , Citoplasma/inmunología , Femenino , Pruebas Hematológicas , Humanos , Inmunoglobulina M/análisis , Cadenas lambda de Inmunoglobulina/análisis , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Linfocitos/inmunología , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/inmunología , Persona de Mediana Edad , Micosis Fungoide/tratamiento farmacológico , Micosis Fungoide/inmunología , Terapia PUVA , Receptores de Antígenos de Linfocitos B/análisis , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/inmunología
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