RESUMO
We have cloned cDNAs coding for human type 2 and type 3 and part of type 1 inositol 1,4,5-trisphosphate receptors (IP3Rs). The complete nucleotide sequences for type 2 and type 3 receptors were determined and the pharmacological properties of the latter were characterized. Human type 2 and type 3 IP3Rs are 2701 amino acids and 2671 amino acids long, respectively, and have significant sequence homologies as well as structural similarities including the six membrane-spanning regions near the C-termini when compared with the rat or mouse counterpart. COS-7 cells transfected with human type 3 IP3R showed characteristic inositol 1,4,5-trisphosphate (IP3)-binding properties with Kd values of 28.8 nM. The order of potency of competition with IP3 was Ins(1,4,5)P3 (IP3) > Ins(2,4,5)P3 > Ins(1,3,4,5)P4 > Ins(1,2,3,4,5,6)P6. Type 2 and type 3 IP3Rs were mapped to human chromosomes 12p11 and 6p21, respectively, by in situ hybridization. cDNA cloning of the human IP3Rs allowed us to identify the types of the receptor expressed in various human hematopoietic and lymphoma cell lines. The type 3 receptor was present in all of cell lines tested, while the type 1 or 2 receptor was expressed in only particular cell types. The differential expression of the IP3R types could confer the cell-specific regulation on the IP3/Ca2+ signalling.
Assuntos
Canais de Cálcio/genética , Inositol 1,4,5-Trifosfato/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Sequência de Aminoácidos , Animais , Sítios de Ligação , Canais de Cálcio/classificação , Canais de Cálcio/metabolismo , Linhagem Celular , Mapeamento Cromossômico , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 6 , Clonagem Molecular , DNA Complementar/genética , Expressão Gênica , Humanos , Receptores de Inositol 1,4,5-Trifosfato , Ligantes , Camundongos , Dados de Sequência Molecular , Ratos , Receptores Citoplasmáticos e Nucleares/classificação , Receptores Citoplasmáticos e Nucleares/metabolismo , Homologia de Sequência de AminoácidosRESUMO
We performed a study of hyperthermia while injecting 0.05% of Noradrenaline following MMC for 10 minutes into the feeding artery of Walker-256 carcinosarcomas implanted 6 days earlier into the s.c. dorsum side of hindpaw of Wistar rats. The tumor growth rates on the 6th day after treatment by warning tumor in hot water (40 degrees C, 44 degrees C) for 10 minutes with or without Noradrenaline, were 0.7 +/- 0.6, 2.1 +/- 0.9 (40 degrees C) and 0.2 +/- 0.3, 0.0 +/- 0.0 (44 degrees C), respectively. The data suggested that tumor ischemia induced by a vasoconstrictive drug may enhance the antitumor effect in low grade warning therapy (40 degrees C). An injection of warmed physiological saline (50 degrees C) may heat the tumor vessels on the tumor surface and showed enhanced antitumor effects as a from of hyperthermia. The target area of the tumor for hyperthermia can be considered to be the tumor vessels on the tumor surface.
Assuntos
Carcinoma 256 de Walker/terapia , Hipertermia Induzida , Mitomicinas/administração & dosagem , Norepinefrina/administração & dosagem , Animais , Carcinoma 256 de Walker/irrigação sanguínea , Carcinoma 256 de Walker/tratamento farmacológico , Terapia Combinada , Hipertermia Induzida/métodos , Injeções Intra-Arteriais , Mitomicina , Mitomicinas/uso terapêutico , Norepinefrina/uso terapêutico , Ratos , Ratos EndogâmicosRESUMO
A 86-year-old man with unresectable pancreatic carcinoma was treated with thermochemotherapy. In most of the body and tail affected by the tumor, which did not show any cytotoxic damage after intraarterial chemotherapy, an enhanced antitumor effect was achieved by hyperthermia, which heated the tumor using hot water in a balloon placed on the pancreas, and which was delivered through a vinyl tube leading out of the body for 40 minutes while administration of antitumor agents mixed with noradrenaline was simultaneously given into the celiac artery. In this case, we observed that using noradrenaline with contrast material injected into the celiac artery it was possible to delineate the tumor area by computed tomography of the pancreas.