Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 96
Filtrar
1.
Am J Trop Med Hyg ; 105(5): 1298-1300, 2021 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-34544038

RESUMEN

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus endemic in many areas around the world. HTLV-1 can induce the development of adult T-cell leukemia (ATL) or myelopathy/tropical spastic paraparesis (HAM/TSP). We report a patient who presented to our outpatient clinic with massive splenomegaly, weight loss, urinary retention, and lower extremity weakness for the previous 3 years. The patient was found to have positive HTLV-1 by ELISA and Western blot from peripheral blood. Evaluation of the spleen demonstrated T-cell large granular lymphocyte leukemia consistent with ATL. In addition to progressive lower extremity weakness, hyperreflexia and clonus, cerebral spinal fluid was positive for HTLV-1 by ELISA and had a reversed CD4-to-CD8 ratio consistent with HAM/TSP. These findings suggest HTLV-1 induced ATL and HAM/TSP presenting simultaneously in the same patient.


Asunto(s)
Antivirales/uso terapéutico , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Leucemia-Linfoma de Células T del Adulto/sangre , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Prednisona/uso terapéutico , Viaje , Humanos , Irán , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Estados Unidos
2.
J Oncol Pharm Pract ; 27(4): 1011-1015, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32869692

RESUMEN

INTRODUCTION: Anthracycline-based chemotherapy regimens are associated with decreased cardiac function with cumulative dosing, yet there is limited information regarding the acute cardiotoxic potential of these medications and appropriate medical management strategies. Herein, we report a case of cardiomyopathy following a single dose of doxorubicin and describe our pharmacologic management approach. CASE REPORT: A 37 year old Jamaican male presented for work-up and treatment of HTLV-1 associated T-cell leukemia/lymphoma. Upon diagnosis, the patient received one cycle of CHOEP, which was complicated by tumor lysis syndrome. Subsequently, the treatment was changed to DA-EPOCH, however, immediately after the initiation of DA-EPOCH on day 1, the patient was found to have t-wave inversions on EKG and an ejection fraction (EF) of 20% with new mitral regurgitation. EPOCH infusion was discontinued within 3 hours of initiation.Management and outcome: The chemotherapy regimen was modified to DA-EPOC with the removal of doxorubicin. The patient was started on metoprolol succinate 12.5 mg once daily for 2 days and subsequently switched to carvedilol 3.125 mg twice daily and lisinopril 5 mg once daily; the patient's ejection fraction improved to baseline after 2.5 months of therapy. DISCUSSION: Though anthracyclines are associated with cardiotoxicity at high cumulative doses, this case highlights the cardiotoxic potential of these medications in the acute setting. Management of anthracycline cardiotoxicity is similar to heart failure management, with data suggesting benefit of using carvedilol and lisinopril. It is unclear if our patient would have benefited from prophylactic angiotensin converting enzymes inhibitors (ACEi) and/or beta-blocker therapy, as he had no known cardiac disease. Acute anthracycline-induced cardiac toxicity is an adverse drug reaction with which providers should be familiar and know how to appropriately manage.


Asunto(s)
Antibióticos Antineoplásicos/efectos adversos , Cardiomiopatías/inducido químicamente , Cardiomiopatías/diagnóstico , Doxorrubicina/efectos adversos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Enfermedad Aguda , Adulto , Antibióticos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cardiomiopatías/fisiopatología , Cardiotoxicidad/diagnóstico , Cardiotoxicidad/etiología , Cardiotoxicidad/fisiopatología , Ciclofosfamida/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Humanos , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Masculino , Prednisona/uso terapéutico , Vincristina/uso terapéutico
3.
Intern Med ; 59(21): 2757-2761, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32641657

RESUMEN

Breast involvement of Adult T-cell leukemia-lymphoma (ATLL) is extremely rare, and the data on the characteristics are limited. We herein describe a 49-year-old woman who presented with skin involvement of ATLL. Positron emission tomography/computed tomography showed bilateral breast lesions. Although the patient once achieved a complete metabolic response, a relapse of her ATLL occurred. The patient received subsequent allogeneic hematopoietic stem cell transplantation (HSCT). To our knowledge, only four cases of ATLL with breast involvement have previously been reported, and the prognoses have generally been poor. Breast lesions of ATLL have aggressive features, and intensive systemic chemotherapy and HSCT are required to improve survival.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/fisiopatología , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/etiología , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Japón , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento
4.
J Clin Exp Hematop ; 59(3): 130-134, 2019 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-31391405

RESUMEN

Hodgkin-like adult T-cell leukemia/lymphoma (ATLL) is a rare variant of ATLL, which represents the early neoplastic phase of ATLL that follows an indolent clinical course compared with typical ATLL. Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disorder characterized by the paralysis of lower limbs and urinary disturbance. Although these diseases are caused by HTLV-1 infection, there are no reports describing the coexistence of Hodgkin-like ATLL and HAM/TSP. Here, we report the first case of Hodgkin-like ATLL complicated by HAM/TSP. The patient was a 56-year-old man with right inguinal lymphadenopathy who had been using the neurology outpatient service for 13 years after being diagnosed with HAM/TSP. He was unable to receive intensive chemotherapy or allogeneic stem cell transplantation due to a poor performance status, but his condition was stable for approximately two years.


Asunto(s)
Enfermedad de Hodgkin , Virus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/fisiopatología , Humanos , Leucemia-Linfoma de Células T del Adulto/sangre , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Masculino , Persona de Mediana Edad , Paraparesia Espástica Tropical/sangre , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/patología , Paraparesia Espástica Tropical/fisiopatología
5.
Adv Ther ; 35(2): 135-152, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29411267

RESUMEN

Adult T-cell leukemia-lymphoma (ATL), a rare and aggressive T-cell malignancy caused by human T-cell lymphotropic virus type 1 (HTLV-1), is associated with a poor prognosis. Evidence-based standard treatment options are lacking and outcomes are generally unsatisfactory, particularly for patients with relapsed or refractory disease. Continued research is contributing to changing treatment landscape as a number of existing and investigational agents are evaluated. We describe the epidemiology of HTLV-1 and ATL, discuss the biology behind the disease, review current treatment practices and guidelines, and provide an overview of emerging therapies in ATL, with a focus on those for relapsed or refractory disease.


Asunto(s)
Leucemia-Linfoma de Células T del Adulto/fisiopatología , Leucemia-Linfoma de Células T del Adulto/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Virus Linfotrópico T Tipo 1 Humano , Humanos , Leucemia-Linfoma de Células T del Adulto/epidemiología , Leucemia-Linfoma de Células T del Adulto/virología
6.
Curr Opin Virol ; 26: 125-131, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28822906

RESUMEN

Human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T-cell leukaemia/lymphoma (ATL), an aggressive CD4+ T-cell malignancy. The mechanisms of leukaemogenesis in ATL are incompletely understood. Insertional mutagenesis has not previously been thought to contribute to the pathogenesis of ATL. However, the recent discovery that HTLV-1 binds the key chromatin architectural protein CTCF raises the hypothesis that HTLV-1 deregulates host gene expression by causing abnormal chromatin looping, bringing the strong HTLV-1 promoter-enhancer near to host genes that lie up to 2Mb from the integrated provirus. Here we review current opinion on the mechanisms of oncogenesis in ATL, with particular emphasis on the local and distant impact of HTLV-1 on the structure and expression of the host genome.


Asunto(s)
Interacciones Huésped-Patógeno , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Mutagénesis Insercional , Provirus/patogenicidad , Factor de Unión a CCCTC/metabolismo , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Unión Proteica , Provirus/genética
7.
Retrovirology ; 13(1): 73, 2016 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-27760548

RESUMEN

BACKGROUND: Exosomes are membrane nano-vesicles secreted by a multitude of cells that harbor biological constituents such as proteins, lipids, mRNA and microRNA. Exosomes can potentially transfer their cargo to other cells, implicating them in many patho-physiological processes. Mesenchymal stem cells (MSCs), residents of the bone marrow and metastatic niches, potentially interact with cancer cells and/or their derived exosomes. In this study, we investigated whether exosomes derived from adult T-cell leukemia/lymphoma (ATL) cells act as intercellular messengers delivering leukemia-related genes that modulate the properties of human MSCs in favor of leukemia. We hypothesized that the cargo of ATL-derived exosomes is transferred to MSCs and alter their functional behavior to support the establishment of the appropriate microenvironment for leukemia. RESULTS: We showed that both ATL cells (C81 and HuT-102) and patient-derived cells released Tax-containing exosomes. The cargo of HuT-102-derived exosomes consisted of miR-21, miR-155 and vascular endothelial growth factor. We demonstrated that HuT-102-derived exosomes not only deliver Tax to recipient MSCs, but also induce NF-κB activation leading to a change in cellular morphology, increase in proliferation and the induction of gene expression of migration and angiogenic markers. CONCLUSIONS: This study demonstrates that ATL-derived exosomes deliver Tax and other leukemia-related genes to MSCs and alter their properties to presumably create a more conducive milieu for leukemia. These findings highlight the contribution of leukemia-derived exosomes in cellular transformation and their potential value as biomarkers and targets in therapeutic strategies.


Asunto(s)
Exosomas/química , Exosomas/fisiología , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Células Madre Mesenquimatosas/fisiología , Adulto , Transporte Biológico , Proliferación Celular , Progresión de la Enfermedad , Exosomas/ultraestructura , Regulación de la Expresión Génica , Productos del Gen tax/genética , Productos del Gen tax/metabolismo , Humanos , Leucemia , Células Madre Mesenquimatosas/química , MicroARNs/genética , MicroARNs/metabolismo , Microscopía Electrónica de Rastreo , FN-kappa B/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
8.
Curr Opin Virol ; 20: 40-46, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27591679

RESUMEN

Human T-cell leukemia virus type 1 (HTLV-1) is a tumorigenic delta retrovirus and the causative infectious agent of a non-Hodgkin's peripheral T-cell malignancy called adult T-cell leukemia/lymphoma (ATL). ATL develops in approximately 5% of infected individuals after a significant clinical latency period of several decades. Clinical classifications of ATL include smoldering, chronic, lymphoma, and acute subtypes, with varying median survival ranges of a few months to several years. Depending on the ATL subtype and disease symptoms, treatment options include 'watchful waiting', chemotherapy, antiviral therapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and targeted therapies. Herein we review the characteristics and development of ATL, as well as current and future treatment options and perspectives.


Asunto(s)
Carcinogénesis , Infecciones por HTLV-I/complicaciones , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Humanos
9.
Retrovirology ; 12: 99, 2015 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-26597716

RESUMEN

BACKGROUND: Adult T-cell leukemia (ATL) is a CD4(+) T-cell neoplasm with a poor prognosis. A previous study has shown that there is a strong correlation between the secreted matricellular protein osteopontin (OPN) level and disease severity in ATL patients. Here, we investigated the role of OPN in ATL pathogenesis and the possible application of anti-OPN monoclonal antibody (mAb) for ATL immunotherapy in NOD/Shi-scid,IL-2Rg (null) (NOG) mice. RESULTS: Subcutaneous inoculation of ATL cell lines into NOG mice increased the plasma level of OPN, which significantly correlated with metastasis of the inoculated cells and survival time. Administration of an SVVYGLR motif-recognizing anti-OPN mAb resulted in inhibition not only of tumor growth but also of tumor invasion and metastasis. The number of fibroblast activating protein-positive fibroblasts was also reduced by this mAb. We then co-inoculated mouse embryonic fibroblasts (MEFs) isolated from wild-type (WT) or OPN knockout mice together with ATL-derived TL-OmI cells into the NOG mice. The mice co-inoculated with WT MEFs displayed a significant decrease in survival relative to those injected with TL-OmI cells alone and the absence of OPN in MEFs markedly improved the survival rate of TL-OmI-inoculated mice. In addition, tumor volume and metastasis were also reduced in the absence of OPN. CONCLUSION: We showed that the xenograft NOG mice model can be a useful system for assessment of the physiological role of OPN in ATL pathogenesis. Using this xenograft model, we found that fibroblast-derived OPN was involved in tumor growth and metastasis, and that this tumor growth and metastasis was significantly suppressed by administration of the anti-OPN mAbs. Our findings will lead to a novel mAb-mediated immunotherapeutic strategy targeting against the interaction of OPN with integrins on the tumor of ATL patients.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Integrinas/metabolismo , Leucemia-Linfoma de Células T del Adulto/terapia , Osteopontina/inmunología , Osteopontina/metabolismo , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Inmunoterapia , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Ganglios Linfáticos/citología , Ganglios Linfáticos/virología , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Osteopontina/sangre , Osteopontina/deficiencia
10.
Immunity ; 42(5): 826-38, 2015 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-25992859

RESUMEN

Interleukin-2 (IL-2) regulates lymphocyte function by signaling through heterodimerization of the IL-2Rß and γc receptor subunits. IL-2 is of considerable therapeutic interest, but harnessing its actions in a controllable manner remains a challenge. Previously, we have engineered an IL-2 "superkine" with enhanced affinity for IL-2Rß. Here, we describe next-generation IL-2 variants that function as "receptor signaling clamps." They retained high affinity for IL-2Rß, inhibiting binding of endogenous IL-2, but their interaction with γc was weakened, attenuating IL-2Rß-γc heterodimerization. These IL-2 analogs acted as partial agonists and differentially affected lymphocytes poised at distinct activation thresholds. Moreover, one variant, H9-RETR, antagonized IL-2 and IL-15 better than blocking antibodies against IL-2Rα or IL-2Rß. Furthermore, this mutein prolonged survival in a model of graft-versus-host disease and blocked spontaneous proliferation of smoldering adult T cell leukemia (ATL) T cells. This receptor-clamping approach might be a general mechanism-based strategy for engineering cytokine partial agonists for therapeutic immunomodulation.


Asunto(s)
Interleucina-2/antagonistas & inhibidores , Ingeniería de Proteínas , Receptores de Interleucina-2/metabolismo , Transducción de Señal/inmunología , Animales , Línea Celular , Proliferación Celular , Femenino , Regulación de la Expresión Génica , Enfermedad Injerto contra Huésped , Humanos , Interleucina-2/química , Interleucina-2/genética , Leucemia-Linfoma de Células T del Adulto/inmunología , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Ratones , Ratones Endogámicos C57BL , Modelos Moleculares , Mutación , Unión Proteica , Estructura Terciaria de Proteína , Receptores de Interleucina-2/química , Factor de Transcripción STAT5/metabolismo , Análisis de Supervivencia
11.
Viruses ; 8(1)2015 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-26729154

RESUMEN

Human T-cell leukemia virus type-1 (HTLV-1) is a tumorigenic retrovirus responsible for development of adult T-cell leukemia/lymphoma (ATLL). This disease manifests after a long clinical latency period of up to 2-3 decades. Two viral gene products, Tax and HBZ, have transforming properties and play a role in the pathogenic process. Genetic and epigenetic cellular changes also occur in HTLV-1-infected cells, which contribute to transformation and disease development. However, the role of cellular factors in transformation is not completely understood. Herein, we examined the role of protein arginine methyltransferase 5 (PRMT5) on HTLV-1-mediated cellular transformation and viral gene expression. We found PRMT5 expression was upregulated during HTLV-1-mediated T-cell transformation, as well as in established lymphocytic leukemia/lymphoma cell lines and ATLL patient PBMCs. shRNA-mediated reduction in PRMT5 protein levels or its inhibition by a small molecule inhibitor (PRMT5i) in HTLV-1-infected lymphocytes resulted in increased viral gene expression and decreased cellular proliferation. PRMT5i also had selective toxicity in HTLV-1-transformed T-cells. Finally, we demonstrated that PRMT5 and the HTLV-1 p30 protein had an additive inhibitory effect on HTLV-1 gene expression. Our study provides evidence for PRMT5 as a host cell factor important in HTLV-1-mediated T-cell transformation, and a potential target for ATLL treatment.


Asunto(s)
Transformación Celular Viral , Virus Linfotrópico T Tipo 1 Humano/fisiología , Leucemia-Linfoma de Células T del Adulto/enzimología , Proteína-Arginina N-Metiltransferasas/metabolismo , Supervivencia Celular , Regulación Viral de la Expresión Génica , Productos del Gen tax/genética , Productos del Gen tax/metabolismo , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Leucemia-Linfoma de Células T del Adulto/genética , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Proteína-Arginina N-Metiltransferasas/genética , Regulación hacia Arriba
12.
Cell Death Dis ; 5: e1575, 2014 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-25522269

RESUMEN

The human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL). HTLV-1 Tax has been shown to have a prosurvival role in infected T cells by enhancing expression of the Bcl-2 family of antiapoptotic proteins. In this study, we show that the expression of proapoptotic BH3-only proteins Bim (Bcl-2-interacting mediator of cell death) and Bid (BH3-interacting domain death agonist) is diminished in HTLV-1-infected leukemic cells. Using a Tax-inducible system and a transient overexpression approach, we demonstrate that Tax downregulates Bid and Bim expression at the transcriptional level. We show that reinforced expression of Bim and Bid in HTLV-1-infected T-cell lines sensitizes CD95/TRAIL- and anticancer drug-induced apoptosis. Furthermore, we show that Tax suppresses Bid and Bim expression by enhancing hypoxia-inducible factor-1α (HIF-1α) protein expression. siRNA knockdown of HIF-1α or chemical inhibition of the transactivation activity of HIF-1α resulted in an increase in Bid and Bim expression and, consequently, in an increase in CD95/TRAIL- and anticancer drug-induced apoptosis in HTLV-1-infected leukemic T-cell lines. Our study provides evidence that besides upregulation of prosurvival Bcl-2 proteins, Tax may also confer apoptosis resistance to HTLV-1-infected T cells by suppressing the expression of the proapoptotic BH3-only proteins Bim and Bid.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/genética , Apoptosis , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/genética , Productos del Gen tax/metabolismo , Virus Linfotrópico T Tipo 1 Humano/metabolismo , Leucemia-Linfoma de Células T del Adulto/genética , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Proteínas de la Membrana/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/metabolismo , Proteína 11 Similar a Bcl2 , Línea Celular , Regulación hacia Abajo , Productos del Gen tax/genética , Interacciones Huésped-Patógeno , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Leucemia-Linfoma de Células T del Adulto/metabolismo , Leucemia-Linfoma de Células T del Adulto/virología , Proteínas de la Membrana/metabolismo , Proteínas Proto-Oncogénicas/metabolismo
13.
Arch Pathol Lab Med ; 138(2): 282-6, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24476526

RESUMEN

Adult T-cell leukemia/lymphoma is a rare mature CD4(+) T-cell neoplasm caused by the retrovirus human T-lymphotrophic virus type 1. At present there are approximately 20 million people infected globally with this virus, and most of these individuals belong to the endemic areas in southern Japan, Africa, the Caribbean basin, and Latin America. In the United States, it is usually seen in immigrants from these endemic regions. Adult T-cell leukemia/lymphoma predominantly affects the adult population and is rare in children. Adult T-cell leukemia/lymphoma has 4 subtypes: acute, lymphomatous, chronic, and smoldering. Clinically, the first 2 variants are classified as aggressive, and the latter two are classified as indolent. Given the rare occurrence and diagnostic challenges associated with adult T-cell leukemia/lymphoma, this review will highlight its salient features to aid in recognition of this entity and perform a comprehensive diagnostic workup.


Asunto(s)
Infecciones por HTLV-I/diagnóstico , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Adulto , Región del Caribe/epidemiología , Diagnóstico Diferencial , Enfermedades Endémicas , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-I/fisiopatología , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/crecimiento & desarrollo , Humanos , Japón/epidemiología , América Latina/epidemiología , Leucemia-Linfoma de Células T del Adulto/epidemiología , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Leucemia-Linfoma de Células T del Adulto/virología , Pronóstico , Estados Unidos/epidemiología
14.
Appl Microbiol Biotechnol ; 89(2): 345-55, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20890756

RESUMEN

Microbial exopolysaccharides (EPSs) are highly heterogeneous polymers produced by fungi and bacteria and have recently been attracting considerable attention from biotechnologists because of their potential applications in many fields, including biomedicine. We have screened the antitumoural activity of a panel of sulphated EPSs produced by a newly discovered species of halophilic bacteria. We found that the novel halophilic bacterium Halomonas stenophila strain B100 produced a heteropolysaccharide that, when oversulphated, exerted antitumoural activity on T cell lines deriving from acute lymphoblastic leukaemia (ALL). Only tumour cells were susceptible to apoptosis induced by the sulphated EPS (B100S), whilst primary T cells were resistant. Moreover, freshly isolated primary cells from the blood of patients with ALL were also susceptible to B100S-induced apoptosis. The newly discovered B100S is therefore the first bacterial EPS that has been demonstrated to exert a potent and selective pro-apoptotic effect on T leukaemia cells, and thus, we propose that the search for new antineoplastic drugs should include the screening of other bacterial EPSs, particularly those isolated from halophiles.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Halomonas/metabolismo , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Polisacáridos Bacterianos/metabolismo , Polisacáridos Bacterianos/farmacología , Cloruro de Sodio/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Halomonas/química , Halomonas/genética , Halomonas/aislamiento & purificación , Humanos , Datos de Secuencia Molecular , Polisacáridos Bacterianos/química , Microbiología del Suelo
15.
Leuk Res ; 34(12): 1617-21, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20211490

RESUMEN

Adult T-cell leukemia/lymphoma is a distinct clinical entity characterized by a clonal proliferation of malignant T-lymphocytes. The etiologic agent of the disease is a Human T-cell lymphotropic virus type I. It occurs almost exclusively in areas where the virus is endemic; however the disease develops only in the minority of patients who are virus carriers. Karyotyping findings and their correlation with clinical features are still limited in T-cell malignancies, complicated by clinical heterogeneity and a plethora of secondary abnormalities. This study describes detailed chromosomal and fluorescence in situ hybridization results observed in a patient with adult T-cell leukemia/lymphoma and correlates them with clinical characteristics.


Asunto(s)
Inestabilidad Genómica , Infecciones por HTLV-I/genética , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto/genética , Linfocitos T , Adulto , Femenino , Infecciones por HTLV-I/patología , Infecciones por HTLV-I/fisiopatología , Humanos , Cariotipificación , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/fisiopatología
18.
Oncogene ; 27(38): 5082-91, 2008 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-18758476

RESUMEN

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subset of ALL with poor clinical outcome compared to B-ALL. Therefore, to improve treatment, it is imperative to delineate the molecular blueprint of this disease. This review describes the central role that the Notch pathway plays in T-ALL development. We also discuss the interactions between Notch and the tumor suppressors Ikaros and p53. Loss of Ikaros, a direct repressor of Notch target genes, and suppression of p53-mediated apoptosis are essential for development of this neoplasm. In addition to the activating mutations of Notch previously described, this review will outline combinations of mutations in pathways that contribute to Notch signaling and appear to drive T-ALL development by 'mimicking' Notch effects on cell cycle and apoptosis.


Asunto(s)
Leucemia-Linfoma de Células T del Adulto/genética , Proteínas de Neoplasias/fisiología , Receptores Notch/fisiología , Linfocitos T/patología , Animales , Apoptosis/fisiología , Ciclo Celular/fisiología , Proteínas F-Box/fisiología , Proteína 7 que Contiene Repeticiones F-Box-WD , Regulación Leucémica de la Expresión Génica , Genes Supresores de Tumor , Humanos , Factor de Transcripción Ikaros/genética , Factor de Transcripción Ikaros/fisiología , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Ligandos , Ratones , Ratones Transgénicos , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Oncogenes , Fosfohidrolasa PTEN/deficiencia , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/fisiología , Receptores Notch/química , Receptores Notch/genética , Transducción de Señal/fisiología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/fisiología , Proteínas Supresoras de Tumor/fisiología , Ubiquitina-Proteína Ligasas/fisiología
19.
J Cutan Pathol ; 35 Suppl 1: 32-7, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18544058

RESUMEN

Adult T-cell leukemia/lymphoma (ATLL) is a rare malignancy caused by human T-cell leukemia virus-1. ATLL is endemic to Japan, and to date, there are only four case reports of patients from Romania who have developed ATLL. Here, we describe a woman living in Madison, Wisconsin, originally from Romania, who presented with an atypical papulosquamous eruption and was ultimately diagnosed with smoldering ATLL. Narrow-band ultraviolet-B (UV-B) therapy and mid-potency topical steroids resulted in skin clearing for approximately 5 months after diagnosis; however, she subsequently relapsed with disease refractory to both narrow band UV-B and psoralen plus ultraviolet A (PUV-A), progressed to acute ATLL and expired secondary to complications.


Asunto(s)
Infecciones por HTLV-I/complicaciones , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Terapia Ultravioleta , Corticoesteroides/uso terapéutico , Adulto , Femenino , Citometría de Flujo , Infecciones por HTLV-I/patología , Infecciones por HTLV-I/fisiopatología , Humanos , Inmunohistoquímica , Leucemia-Linfoma de Células T del Adulto/radioterapia , Reacción en Cadena de la Polimerasa , Infecciones del Sistema Respiratorio/patología , Rumanía , Vitíligo/patología
20.
Braz J Med Biol Res ; 41(5): 344-50, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18488097

RESUMEN

T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous disease with respect to phenotype, gene expression profile and activation of particular intracellular signaling pathways. Despite very significant improvements, current therapeutic regimens still fail to cure a portion of the patients and frequently implicate the use of aggressive protocols with long-term side effects. In this review, we focused on how deregulation of critical signaling pathways, in particular Notch, PI3K/Akt, MAPK, Jak/STAT and TGF-beta, may contribute to T-ALL. Identifying the alterations that affect intracellular pathways that regulate cell cycle and apoptosis is essential to understanding the biology of this malignancy, to define more effective markers for the correct stratification of patients into appropriate therapeutic regimens and to identify novel targets for the development of specific, less detrimental therapies for T-ALL.


Asunto(s)
Diferenciación Celular , Leucemia-Linfoma de Células T del Adulto , Fosfotransferasas/fisiología , Transducción de Señal/fisiología , Linfocitos T/citología , Humanos , Quinasas Janus/fisiología , Leucemia-Linfoma de Células T del Adulto/etiología , Leucemia-Linfoma de Células T del Adulto/fisiopatología , Leucemia-Linfoma de Células T del Adulto/terapia , Proteínas Quinasas Activadas por Mitógenos/fisiología , Fosfatidilinositol 3-Quinasas/fisiología , Fosforilación , Proteínas Proto-Oncogénicas c-akt/fisiología , Receptores Notch/fisiología , Factor de Crecimiento Transformador beta/fisiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...