RESUMO
Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain tumor. We report a case of embryonal tumor with multilayered rosettes in the parietooccipital region of a 2-year-old girl. Histopathology of the tumor demonstrated amplification of the 19q13.42 locus and strong positivity for LIN28A. Treatment was multimodal and included 3 surgical resections, adjuvant chemotherapy with autologous stem cell rescue, and focal radiotherapy. The use of the agents vorinostat and isotretinoin, and the addition of focal radiation have not been extensively described in this patient population, but may attribute to our patient's sustained remission at 2.5-years follow-up.
Assuntos
Neoplasias Encefálicas , Cromossomos Humanos Par 19/genética , Loci Gênicos , Isotretinoína/administração & dosagem , Neoplasias Embrionárias de Células Germinativas , Transplante de Células-Tronco , Vorinostat/administração & dosagem , Autoenxertos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Quimiorradioterapia Adjuvante , Pré-Escolar , Feminino , Humanos , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapiaRESUMO
Hepatocellular carcinoma (HCC) is a highly fatal form of liver cancer. Recently, the interest in using amino acids as therapeutic agents has noticeably grown. The present work aimed to evaluate the possible antiproliferative effects of selected amino acids supplementation or deprivation in human HCC cell lines and to investigate their effects on critical signaling molecules in HCC pathogenesis and the outcomes of their combination with the histone deacetylase inhibitor vorinostat. HepG2 and Huh7 cells were treated with different concentrations of L-leucine, L-glutamine, or L-methionine and cell viability was determined using MTT assay. Insulin-like growth factor 1 (IGF1), phosphorylated ribosomal protein S6 kinase (p70 S6K), p53, and cyclin D1 (CD1) protein levels were assayed using ELISA. Caspase-3 activity was assessed colorimetrically. L-leucine supplementation (0.8-102.4 mM) and L-glutamine supplementation (4-128 mM) showed dose-dependent antiproliferative effects in both cell lines but L-methionine supplementation (0.2-25.6 mM) only affected the viability of HepG2 cells. Glutamine or methionine deprivation suppressed the proliferation of HepG2 cells whereas leucine deprivation had no effect on cell viability in both cell lines. The combination between the effective antiproliferative changes in L-leucine, L-glutamine, and L-methionine concentrations greatly suppressed cell viability and increased the sensitivity to vorinostat in both cell lines. The growth inhibitory effects were paralleled with significant decreases in IGF-1, phospho p70 S6k, and CD1 levels and significant elevations in p53 and caspase-3 activity. Changes in amino acids concentrations could profoundly affect growth in HCC cell lines and their response to epigenetic therapy.
Assuntos
Aminoácidos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Vorinostat/farmacologia , Aminoácidos/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Epigênese Genética , Células Hep G2 , Inibidores de Histona Desacetilases/administração & dosagem , Inibidores de Histona Desacetilases/farmacologia , Humanos , Neoplasias Hepáticas/genética , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Vorinostat/administração & dosagemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Bortezomib/administração & dosagem , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Sorafenibe/administração & dosagem , Vorinostat/administração & dosagemRESUMO
Photoreceptor cell death in inherited retinal degeneration is accompanied by over-activation of histone deacetylases (HDAC). Excessive HDAC activity is found both in primary rod degeneration (such as in the rd10 mouse) and in primary cone death, including the cone photoreceptor function loss 1 (cpfl1) mouse. We evaluated the potential of pharmacological HDAC inhibition to prevent photoreceptor degeneration in primary rod and cone degeneration. We show that a single in vivo treatment of cpfl1 mice with the HDAC inhibitor trichostatin A (TSA) resulted in a significant protection of cpfl1 mutant cones. Similarly, HDAC inhibition with the clinically approved HDAC inhibitor vorinostat (SAHA) resulted in a significant improvement of rod survival in rd10 retinal explant cultures. Altogether, these results highlight the feasibility of targeted neuroprotection in vivo and create hope to maintain vision in patients suffering from both rod and cone dystrophies.