RESUMO
BACKGROUND: Osteosarcoma treatment failure is most often from the inability to control metastatic disease in the lungs. Encapsulating cisplatin within lipid complexes and delivering the agent via inhalation targets lung metastases with minimal systemic exposure. An open-label, phase Ib/IIa study was performed to characterize the safety and efficacy of inhaled lipid cisplatin (ILC) in recurrent osteosarcoma patients who only had pulmonary metastases. PROCEDURE: ILC was administered via nebulizer every 2 weeks (=1 cycle). Response was evaluated radiographically every 2 cycles. Cisplatin levels were measured in patients. When possible, metastasectomy was undertaken in patients after 2 cycles. RESULTS: Nineteen patients were treated. No patients experienced hematologic toxicity, nephrotoxicity or ototoxicity. Nausea/vomiting (≥grade 3) was attributed to study drug in one patient. Respiratory symptoms were observed in 13/19 patients with only one patient experiencing a ≥grade 3 respiratory symptom (not related to study drug). Systemic cisplatin exposure was minimal. Eleven patients had bulky disease, and all progressed prior to cycle 7. Eight patients had all lesions ≤2 cm. One patient had a sustained partial response. An additional two patients had stable disease after 2 cycles, underwent metastasectomy, and remained free from pulmonary recurrence 1 year after initiation of therapy. CONCLUSIONS: ILC is well tolerated in heavily treated osteosarcoma patients and did not appear to have the typical toxicities associated with intravenous cisplatin. Three of eight patients with less bulky disease had sustained benefit. Further study of ILC is warranted.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Cisplatino/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Administração por Inalação , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/patologia , Química Farmacêutica , Cisplatino/efeitos adversos , Feminino , Humanos , Lipídeos/administração & dosagem , Neoplasias Pulmonares/secundário , Masculino , Osteossarcoma/secundário , Adulto JovemRESUMO
Gemella morbillorum and Gemella haemolysans are normal oral flora that can also be pathogenic. We report 2 cases of adolescents with osteosarcoma who developed multiple pulmonary nodules associated with Gemella bacteremia. These nodules mimicked metastatic disease. To our knowledge, this manifestation of Gemella infection has not been previously reported. In the setting of malignancy, infectious pulmonary nodules must be distinguished from metastatic nodules in order to treat appropriately.
Assuntos
Neoplasias Ósseas/complicações , Infecções por Bactérias Gram-Positivas/diagnóstico , Pneumopatias/diagnóstico , Pneumopatias/microbiologia , Neoplasias Pulmonares/diagnóstico , Osteossarcoma/complicações , Staphylococcaceae/isolamento & purificação , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Diagnóstico Diferencial , Evolução Fatal , Feminino , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Pneumopatias/complicações , Neoplasias Pulmonares/secundário , Masculino , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Insuficiência Respiratória/complicações , Tomografia Computadorizada por Raios X/métodosRESUMO
EWS-WT1 is a chimeric transcription factor resulting from fusion of the N-terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc fingers of the Wilms tumor suppressor WT1. This translocation underlies desmoplastic small round cell tumor (DSRCT), which is noted for the abundance of reactive stroma surrounding islets of tumor cells, suggestive of paracrine signals contributing to tumor cell proliferation. Hybridization to high-density oligonucleotide microarrays can be used to identify targets of EWS-WT1. Expression of EWS-WT1 from a tetracycline-regulated promoter leads to the induction of growth-associated genes, of which the most remarkable is the beta-chain of the interleukin-2/15 receptor (IL-2/15Rbeta). Potent transcriptional activation by the chimeric protein maps to two bindings sites within the IL-2/15Rbeta promoter. Analysis of primary DSRCT tumor specimens demonstrates high levels of IL-2/15Rbeta within the tumor cells, along with expression of IL-2 and IL-15 by the abundant hyperplastic endothelial cells within the reactive stroma. Activation of this cytokine signaling pathway is consistent with the nuclear localization of its downstream effectors, phosphorylated STAT3 and STAT5. These observations suggest that the transcriptional induction of a cytokine receptor by a tumor-associated translocation product enables a proliferative response of epithelial cancer cells to ligands secreted by the surrounding stroma.
Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas do Leite , Proteínas de Fusão Oncogênica/metabolismo , Receptores de Interleucina/genética , Neoplasias Abdominais/genética , Neoplasias Abdominais/metabolismo , Neoplasias Abdominais/patologia , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/patologia , Proteínas de Ligação a DNA/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Humanos , Imuno-Histoquímica , Interleucina-2/metabolismo , Subunidade beta de Receptor de Interleucina-2 , Interleucina-5/metabolismo , Janus Quinase 1 , Janus Quinase 3 , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas de Fusão Oncogênica/genética , Regiões Promotoras Genéticas , Proteínas Tirosina Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Interleucina/biossíntese , Receptores de Interleucina/metabolismo , Receptores de Interleucina-15 , Receptores de Interleucina-2/metabolismo , Elementos de Resposta/genética , Fator de Transcrição STAT3 , Fator de Transcrição STAT5 , Transdução de Sinais , Transativadores/metabolismo , Transcrição Gênica , Células Tumorais CultivadasRESUMO
Congenital self-healing reticulohistiocytosis, also known as congenital self-healing Langerhans cell histiocytosis or Hashimoto-Pritzker disease, is a Langerhans cell histiocytosis. It is characterized by skin lesions in the newborn period in an otherwise healthy infant that show a Langerhans cell infiltrate in the skin on histological analysis. These findings subsequently spontaneously involute. This report describes two newborns who presented at birth with differing presentations of congenital self-healing reticulohistiocytosis. A review of the disorder, including diagnosis and evaluation, is presented.