RESUMO
PIM serine/threonine kinases are overexpressed, translocated, or amplified in multiple B-cell lymphoma types. We have explored the frequency and relevance of PIM expression in different B-cell lymphoma types and investigated whether PIM inhibition could be a rational therapeutic approach. Increased expression of PIM2 was detected in subsets of mantle cell lymphoma, diffuse large B-cell lymphoma (DLBLC), follicular lymphoma, marginal zone lymphoma-mucosa-associated lymphoid tissue type, chronic lymphocytic leukemia, and nodal marginal zone lymphoma cases. Increased PIM2 protein expression was associated with an aggressive clinical course in activated B-like-DLBCL patients. Pharmacologic and genetic inhibition of PIM2 revealed p4E-BP1(Thr37/46) and p4E-BP1(Ser65) as molecular biomarkers characteristic of PIM2 activity and indicated the involvement of PIM2 kinase in regulating mammalian target of rapamycin complex 1. The simultaneous genetic inhibition of all 3 PIM kinases induced changes in apoptosis and cell cycle. In conclusion, we show that PIM2 kinase inhibition is a rational approach in DLBCL treatment, identify appropriate biomarkers for pharmacodynamic studies, and provide a new marker for patient stratification.
Assuntos
Inibidores Enzimáticos/farmacologia , Terapia Genética/métodos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Linfonodos/patologia , Linfoma Folicular/genética , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Linfoma Difuso de Grandes Células B/patologia , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Tonsila Palatina/patologia , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
We studied the taxonomy of Pluteus podospileus and similar species using morphological and molecular (nrITS, TEF1-α) data, including a detailed study of the type collections of P. inflatus var. alneus, Pluteus minutissimus f. major, and P. granulatus var. tenellus. Within the P. podospileus complex, we phylogenetically confirmed six species in Europe, five in Asia, and eight in North America. Based on our results, we recognize P. seticeps as a separate species occurring in North America, while P. podospileus is limited to Eurasia. We describe six new species and a new variety: P. absconditus, P. fuscodiscus, P. gausapatus, P. inexpectatus, P. millsii, and P. notabilis and its variety, P. notabilis var. insignis. We elevate Pluteus seticeps var. cystidiosus to species rank as Pluteus cystidiosus. Based on the holotype of P. inflatus var. alneus, collections of P. inflatus identified by Velenovský, and several modern collections, we resurrect the name P. inflatus. Based on molecular analyses of syntypes of Pluteus minutissimus f. major and a holotype of Pluteus granulatus var. tenellus, we synonymize them under P. inflatus. We also increase our knowledge about the morphology and distribution of P. cutefractus.
Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Linfoma Folicular/patologia , Recidiva Local de Neoplasia/patologia , Couro Cabeludo , Neoplasias Cutâneas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Linfoma Folicular/terapia , Pessoa de Meia-Idade , Neoplasias Cutâneas/terapia , Conduta ExpectanteRESUMO
The most frequent location for non-metastatic germ cell tumors is the anterior mediastinum. Primary lung germ cell tumors are an exception in medical literature being limited to just a few cases of choriocarcinomas and rare cases of yolk-sac tumors. In this paper, we report a case of a pulmonary yolk-sac tumor with atypical characteristic as regards its diagnosis and treatment.
Assuntos
Tumor do Seio Endodérmico/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma , Idoso , Biomarcadores Tumorais/análise , Carcinoma Basocelular , Tumor do Seio Endodérmico/química , Tumor do Seio Endodérmico/diagnóstico , Tumor do Seio Endodérmico/epidemiologia , Tumor do Seio Endodérmico/cirurgia , Neoplasias Faciais , Humanos , Achados Incidentais , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/cirurgia , Masculino , Segunda Neoplasia Primária , Pneumonectomia , Neoplasias Retais , Neoplasias Cutâneas , ToracotomiaAssuntos
Neoplasias do Colo/complicações , Neoplasias do Colo/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/patologia , Lipoma/complicações , Lipoma/diagnóstico , Neoplasias do Colo/cirurgia , Diagnóstico Diferencial , Hemorragia Gastrointestinal/diagnóstico por imagem , Humanos , Lipoma/cirurgia , Masculino , Pessoa de Meia-Idade , RadiografiaAssuntos
Hemangiossarcoma/secundário , Neoplasias Pulmonares/secundário , Neoplasias do Mediastino/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Dispneia/etiologia , Hemangiossarcoma/complicações , Hemangiossarcoma/diagnóstico por imagem , Hemoptise/etiologia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Neoplasias do Mediastino/patologia , Pessoa de Meia-IdadeRESUMO
La localización intratorácica más frecuente para los tumores germinales no metastáticos, es el mediastino anterior. Los tumores de células germinales primarios de pulmón son una excepción en la literatura limitándose a algunos casos de coriocarcinomas y raros casos de tumores del seno endodérmico. En este artículo, se presenta un caso de tumor del seno endodérmico primario de pulmón de características atípicas en cuanto a la manera de diagnostico y al tratamiento practicado(AU)
The most frequent location for non-metastatic germ cell tumors is the anterior mediastinum. Primary lung germ cell tumors are an exception in medical literature being limited to just a few cases of choriocarcinomas and rare cases of yolk-sac tumors. In this paper, we report a case of a pulmonary yolk-sac tumor with atypical characteristic as regards its diagnosis and treatment(AU)