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1.
Handb Clin Neurol ; 202: 239-247, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39111910

RESUMEN

Recent advances in neuroimmunology have shed light on the pathogenic mechanisms underlying rare neuroimmunologic conditions such as myasthenia gravis (MG) and stiff person syndrome (SPS). Despite the rarity of these conditions, their complex manifestations and potential for irreversible disability necessitate effective therapeutic strategies. This chapter reviews the current understanding of the safety and efficacy of hematopoietic stem cell transplantation (HSCT) in MG and SPS. Several case reports and retrospective studies have demonstrated promising outcomes following HSCT in refractory MG and SPS, with significant clinical improvement and even discontinuation of chronic immunomodulatory therapy in some cases. Furthermore, HSCT may offer insights into the underlying pathophysiologic mechanisms of these conditions, particularly the role of cellular immunity. Although more research is needed to fully understand the impact of HSCT on disease pathology and outcomes, current evidence suggests that HSCT could be a valuable therapeutic option for patients with refractory MG and SPS.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Miastenia Gravis , Síndrome de la Persona Rígida , Síndrome de la Persona Rígida/terapia , Humanos , Miastenia Gravis/terapia , Trasplante de Células Madre Hematopoyéticas/métodos
2.
Mult Scler ; 29(13): 1688-1692, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37712415

RESUMEN

Cortical lesions (CLs) detected with double inversion recovery (DIR) magnetic resonance imaging (MRI) are very helpful in differentiating multiple sclerosis (MS) from other neuroinflammatory diseases of the central nervous system (CNS), that is, neuromyelitis optica spectrum disorders (NMOSDs). Furthermore, CLs are closely related to motor and cognitive impairment. We report a case of a 48-year-old female MS patient who developed several CLs during anti-CD20 therapy. Some CLs disappeared during follow-up MRIs. In the suspicion of a treatment failure, the screening for the autologous hematopoietic stem cell transplant (AHSCT) was performed with the evidence of an atrial myxoma. In MS patients with new CLs, a comorbid ischemic pathology should be considered and carefully investigated.


Asunto(s)
Fibrilación Atrial , Esclerosis Múltiple , Mixoma , Neuromielitis Óptica , Femenino , Humanos , Persona de Mediana Edad , Fibrilación Atrial/patología , Corteza Cerebral/patología , Esclerosis Múltiple/patología , Neuromielitis Óptica/patología , Imagen por Resonancia Magnética/métodos , Mixoma/diagnóstico por imagen , Mixoma/patología
3.
Anticancer Res ; 22(6B): 3555-9, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12552955

RESUMEN

BACKGROUND: Neoadjuvant chemotherapy for intermediate/high-grade soft tissue sarcomas (STS) may provide some advantages for facilitating the surgical resection of the tumor and for disease control. However its role as induction therapy before surgery should still be proved. PATIENTS AND METHODS: Twenty-one patients with intermediate/high-grade STS and tumor size > or = 5 cm were consecutively treated from 1997 to 2001 with neoadjuvant chemotherapy based on epirubicin 60 mg/m2/day on days 1 and 2 and ifosfamide 1.8 gr/m2/day on days 1 through 5 every three weeks. Evaluation of objective tumor response and toxicity were carried out according to WHO criteria. RESULTS: Nine partial responses were documented; stable disease in 11 patients, progressive disease in one patient. Apart from nine cases of grade 4 neutropenia, the treatment was generally well-tolerated. Twelve patients underwent conservative and limb salvage surgery. CONCLUSION: This therapeutic approach seems to be effective in facilitating surgery. Neutropenia was the most significant toxicity but it was preventable or medically treatable with G-CSF support.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Adulto , Anciano , Supervivencia sin Enfermedad , Epirrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Ifosfamida/administración & dosificación , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Sarcoma/patología , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/cirugía
4.
Mol Cell Endocrinol ; 165(1-2): 199-209, 2000 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-10940498

RESUMEN

Antiestrogens are widely used for breast cancer treatment, where they act primarily by inhibiting the mitogenic action of estrogens on tumor cells. The effects of the pure antiestrogen ICI 182,780 on estrogen-regulated cell cycle phase-specific events were investigated here in synchronously cycling human breast cancer (HBC) cells. In early G(1)-arrested MCF-7 or ZR-75.1 cells, 17beta-estradiol (E2) induces rapid activation of the cyclin/Cdk/pRb pathway, as demonstrated by D-type G(1) cyclins accumulation during the first few hours of hormonal stimulation, followed by sequential accumulation of E, A and B1 cyclins and progressive pRb phosphorylation, as cells progress through the cell cycle. When added to quiescent cells together with E2, ICI 182,780 prevents all of the above hormonal effects. Interestingly, in mid-G(1) cells (2-8 h into estrogen stimulation) the antiestrogen causes rapid reversal of hormone-induced D-type cyclins accumulation and pRb phosphorylation, and still fully inhibits G(1)-S transition rate, while in late-G(1) cells it does not prevent S phase entry but still inhibits significantly DNA synthesis rate, S-phase cyclins accumulation and pRb hyperphosphorylation. These results indicate that pure antiestrogens prevent multiple estrogen-induced cell cycle-regulatory events, each timed to allow efficient G(1) completion, G(1)-S transition, DNA synthesis and cell cycle completion.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Estradiol/análogos & derivados , Moduladores de los Receptores de Estrógeno/farmacología , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias Hormono-Dependientes/patología , Neoplasias de la Mama/metabolismo , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , División Celular/efectos de los fármacos , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/metabolismo , Estradiol/farmacología , Estrógenos/metabolismo , Femenino , Fulvestrant , Humanos , Neoplasias Hormono-Dependientes/metabolismo , Fosforilación , Proteína de Retinoblastoma/metabolismo , Células Tumorales Cultivadas
5.
Proc Natl Acad Sci U S A ; 93(10): 4629-32, 1996 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-8643454

RESUMEN

The human Rb2/p130 gene shares many structural and functional features with the retinoblastoma gene and the retinoblastoma-related p107 gene. In the present study, we have cloned and partially sequenced the gene coding for the Rb2/p130 protein from human genomic libraries. The complete intron-exon organization of this gene has been elucidated. The gene contains 22 exons spanning over 50 kb of genomic DNA. The length of individual exons ranges from 65 to 1517 bp. The largest intron spans over 9 kb, and the smallest has only 82 bp. The 5' flanking region revealed a structural organization characteristic of promoters of "housekeeping" and growth control-related genes. A typical TATA or CAAT box is not present, but there are several GC boxes and potential binding sites for numerous transcription factors. This study provides the molecular basis for understanding the transcriptional control of the Rb2/p130 gene and for implementing a comprehensive Rb2/p130 mutation screen using genomic DNA as a template.


Asunto(s)
Neoplasias del Ojo/genética , Genes de Retinoblastoma , Fosfoproteínas/genética , Proteínas , Proteína de Retinoblastoma/genética , Retinoblastoma/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN de Neoplasias/genética , Exones , Humanos , Intrones , Datos de Secuencia Molecular , Proteína p130 Similar a la del Retinoblastoma
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