RESUMEN
PPM [metal-dependent protein phosphatase, formerly called PP2C (protein phosphatase 2C)] family members play essential roles in regulating a variety of signalling pathways. While searching for protein phosphatase(s) that act on AMPK (AMP-activated protein kinase), we found that PPM1A and PPM1B are N-myristoylated and that this modification is essential for their ability to dephosphorylate the α subunit of AMPK (AMPKα) in cells. N-Myristoylation was also required for two other functions of PPM1A and PPM1B in cells. Although a non-myristoylated mutation (G2A) of PPM1A and PPM1B prevented membrane association, this relocalization did not likely cause the decreased activity towards AMPKα. In in vitro experiments, the G2A mutants exhibited reduced activities towards AMPKα, but much higher specific activity against an artificial substrate, PNPP (p-nitrophenyl phosphate), compared with the wild-type counterparts. Taken together, the results of the present study suggest that N-myristoylation of PPM1A and PPM1B plays a key role in recognition of their physiological substrates in cells.
Asunto(s)
Fosfoproteínas Fosfatasas/metabolismo , Proteínas Quinasas Activadas por AMP/química , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Secuencia de Bases , Dominio Catalítico/genética , Células HEK293 , Células HeLa , Humanos , Ratones , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Ácido Mirístico/metabolismo , Nitrofenoles/metabolismo , Compuestos Organofosforados/metabolismo , Fosfoproteínas Fosfatasas/química , Fosfoproteínas Fosfatasas/genética , Fosforilación , Proteína Fosfatasa 2C , Procesamiento Proteico-Postraduccional , ARN Interferente Pequeño/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidad por SustratoRESUMEN
Salivary ductcarcinoma (SDC)is a high-grade malignant tumor arising predominantly in the parotid gland. Androgen receptor(AR)expression was mainly restricted to SDC in salivary cancer. We report successful treatment of a patient with advanced SDC using an endocrine chemotherapy. A 76-year-old man was hospitalized with lumbalgia and swelling of left submandibular region. Radiological examination indicated a tumor in left submandibular gland and metastatic tumors in lumbar vertebra, accompanied by swollen lymph nodes of the neck, mediastinum. Needle biopsies of both vertebral tumor and cervical lymph node revealed SDC. Positive nuclear staining was observed against AR in tumor cells of our patient by immunohistochemical analysis. He obtained a partial response after 1 course of treatment with both anti-androgen therapy and palliative chemotherapy using paclitaxel. In contrast to previous reports of poor response to chemotherapy alone and short-term survival of patients with SDC, our patient has demonstrated that chemotherapy combined with anti-androgen therapy may be an effective modality as a therapeutic regimen for SDC.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma Ductal/tratamiento farmacológico , Hormona Liberadora de Gonadotropina/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias de las Glándulas Salivales/tratamiento farmacológico , Anciano , Antagonistas de Andrógenos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Biopsia , Carcinoma Ductal/patología , Hormona Liberadora de Gonadotropina/administración & dosificación , Hormona Liberadora de Gonadotropina/análogos & derivados , Humanos , Masculino , Paclitaxel/administración & dosificación , Neoplasias de las Glándulas Salivales/patología , Tomografía Computarizada por Rayos XRESUMEN
Zygomycosis is an opportunistic fungal infection that affects the central nervous system (CNS). In this report, we present three cases of zygomycosis with CNS involvement. In two patients zygomycosis developed after neurosurgery, and in the third patient zygomycosis developed after bone marrow transplantation for leukemia. All patients developed persistent fever and neurological deficits. They presented with progressive cerebral infarction accompanied by hemorrhage. Intraoperative findings and histopathological examinations revealed that zygomycotic hyphae caused mycotic aneurysm, vasculitis, and venous occlusion.
Asunto(s)
Encefalopatías/etiología , Cigomicosis/etiología , Adulto , Anciano , Trasplante de Médula Ósea , Encefalopatías/diagnóstico por imagen , Infarto Cerebral/etiología , Femenino , Humanos , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Infecciones Oportunistas , Complicaciones Posoperatorias , Radiografía , Cigomicosis/diagnóstico por imagenAsunto(s)
Mastocitosis Sistémica/tratamiento farmacológico , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Anciano , Benzamidas , Codón/genética , Humanos , Mesilato de Imatinib , Masculino , Mastocitosis Sistémica/genética , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Resultado del TratamientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tumor Carcinoide/terapia , Neoplasias del Recto/terapia , Recto/cirugía , Neoplasias de los Tejidos Blandos/secundario , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Irinotecán , Leucovorina/administración & dosificación , Persona de Mediana Edad , Inducción de Remisión , Neoplasias de los Tejidos Blandos/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
We present a case of squamous cell carcinoma of the testis that metastasized from lung cancer. The patient, who had received left pneumonectomy 2 years earlier for squamous cell carcinoma (SCC) of the lung, developed pulmonary metastasis, which was treated with chemotherapy. Although the recurrence regressed after treatment, the testicular tumor progressed gradually. Left radical orchiectomy was performed. Pathological examination revealed metastatic SCC. Testicular metastasis from lung cancer is a very rare disease.