Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/patologia , Linfoma não Hodgkin/patologia , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/efeitos dos fármacos , Gânglios da Base/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Criança , Citarabina/administração & dosagem , Humanos , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Melfalan/administração & dosagem , Metotrexato/administração & dosagem , Radiografia , Tálamo/diagnóstico por imagem , Tálamo/efeitos dos fármacos , Tálamo/patologia , Tiotepa/administração & dosagem , Substância Branca/diagnóstico por imagem , Substância Branca/efeitos dos fármacos , Substância Branca/patologiaRESUMO
BACKGROUND: A combination of 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX) is a standard regimen for the chemotherapy of metastatic colorectal cancer. The major dose-limiting toxic effect of oxaliplatin is neurotoxicity. The aim of this study was to evaluate the preventive effects of traditional Japanese medicines, goshajinkigan and shakuyakukanzoto on oxaliplatin-induced neurotoxicity with FOLFOX. PATIENTS AND METHODS: Between July 2006 and November 2008, a total of 44 patients with metastatic colorectal cancer received modified FOLFOX6 or FOLFOX4, as first-line chemotherapy at three institutions. They concurrently received either goshajinkigan (group A, n=20) or shakuyakukanzoto (group B, n=24) for neurotoxicity reduction. RESULTS: The median number of treatment cycles and the median cumulative dose of oxaliplatin were 12 cycles (range, 4-19) and 898 mg/m(2) (range, 340-1255) in group A and 10.5 cycles (range, 6-20) and 845 mg/m(2) (range, 510-1480) in group B. Eighteen patients in group A and 24 in group B received oxaliplatin in a cumulative dose exceeding 500 mg/m(2). At a dose of 500 mg/m(2) oxaliplatin, grade 1-2 toxicity occurred in 10 patients of group A and in 7 of group B, but there was no grade 3 or higher toxicity in either group. The response rate of the 38 patients with measurable lesions was 50.0% (9/18) in group A and 65% (13/20) in group B. CONCLUSION: The administration of traditional Japanese medicine may reduce oxalipatin-induced neurotoxicity without negatively affecting tumor response in patients with colorectal cancer who undergo FOLFOX therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Síndromes Neurotóxicas/prevenção & controle , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Glycyrrhiza , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Síndromes Neurotóxicas/etiologia , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Paeonia , Estudos RetrospectivosRESUMO
Urotensin II (UII) has been reported as the most potent known vasoconstrictor. While rat and mouse orthologs of UII precursor protein have been reported, only the tentative structures of UII peptides of these animals have been demonstrated, since prepro-UII proteins lack typical processing sites for their mature peptides. In the present study, we isolated a novel peptide, UII-related peptide (URP), from the extract of the rat brain as the sole immunoreactive substance to anti-UII antibody; the amino acid sequence of the peptide was determined as ACFWKYCV. cDNAs encoding rat, mouse, and human precursor proteins for URP were cloned and revealed that the sequences of mouse and human URP peptides are the same as that for rat URP. Prepro-URP gene is expressed in several rat tissues such as those of the thymus, spleen, testis, and spinal cord, although with lower levels than the prepro-UII gene. In the human, the prepro-URP gene is expressed comparably to prepro-UII in several tissues except the spinal cord. URP was found to bind and activate the human or rat UII receptors (GPR14) and showed a hypotensive effect when administered to anesthetized rats. These results suggest that URP is the endogenous and functional ligand for UII receptor in the rat and mouse, and possibly in the human. We also describe the preparation of specific monoclonal antibodies raised against UII peptide and the establishment of a highly sensitive enzyme immunoassay system for UII peptides.