RESUMO
BACKGROUND/AIM: Boron tracedrugs possess global molecular tracking abilities and localized destructive power. We investigated the molecular properties of synthesized boron tracedrugs, including UTX-51, and their interactions with the advanced glycation end-product (AGE)-related protein bovine serum albumin (BSA). MATERIALS AND METHODS: A conformational analysis of the compounds used in the present study was performed using CAChe (Fujitsu Inc., Tokyo, Japan) and the degree of stereo-hydrophobicity of the conformers obtained was verified using Mopac (Fujitsu Inc.). The interactive properties of global minimum conformers of the derivatives tested with BSA were assessed using Molegro Virtual Docker (CLC bio., Aarhus, Denmark). RESULTS: Among the compounds investigated, UTX-51 was confirmed to interact with BSA based on the formation of hydrogen bonds between BSA and UTX-51. CONCLUSION: UTX-51 is a promising boron tracedrug and can be used as the lead structure for developing a therapeutic agent for AGE-related diseases, including cancer.
Assuntos
Terapia por Captura de Nêutron de Boro , Boro , Boro/uso terapêutico , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Japão , Nêutrons , Soroalbumina BovinaRESUMO
BACKGROUND: From the design and synthesis of enantiomers, we can expect to obtain two compounds with different pharmacokinetics and pharmacological activities at the same time, which is thought to lead to the development of efficient anticancer agents. Chiral-2-nitroimidazole TX-2036 derivatives exhibit stereo-configuration (R- and S-configuration)-dependent tyrosine kinase inhibitory activity, and the activity of the tyrosine kinase domain of EGF receptor (EGFR-tyk) is suppressed. In order to clarify the reason why the effects on EGFR-tyk activity differ depending on stereoisomers, we tried to analyze the interaction between each TX-2036 derivative and EGFR-tyk. MATERIALS AND METHODS: The 2-nitroimidazole-based radiosensitizer TX-2036 series were synthesized and their molecular features were examined using protein kinase inhibition assay and molecular structural analysis. RESULTS: R-configured TXs (TX-2043, -2030, and -2036) exhibited more potent protein kinase inhibitory activity than S-configured TXs (TX-2044, - 2031, and -2037), and the IC50 value of TX-2036 was 1.8 µM. CONCLUSION: R-configured TXs interacted with Lys721 and Thr766 of EGFR-tyk. The combinations of amino acid residues targeted by the S-configured TXs were different from each other (Ile765 and Thr766 (TX-2044), Ser696, Thr766, and Thr830 (TX-2031), Gly772, Cys773, and Thr830 (TX-2037)). Preparing a series of isomers with different target sites was considered beneficial when the target was mutated.
Assuntos
Domínios Proteicos/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Humanos , Isomerismo , Radiossensibilizantes/farmacologia , EstereoisomerismoRESUMO
BACKGROUND/AIM: The stereo-configuration (R-, S-configuration) of chiral-2-nitroimidazole derivatives alters their radiosensitizing activity. This study aimed at examining the molecular features of these enantiomers by molecular simulation techniques. MATERIALS AND METHODS: A series of 2-nitroimidazole-based radiosensitizer TX-2036 molecules were synthesized, and their profiles were examined using molecular structural analysis such as conformation analysis, molecular orbital analysis, and electrostatic potential analysis. RESULTS: R-configured TXs (TX-2043, -2030, -2036) had a weaker radiosensitizing activity than S-configured TXs (TX-2044, -2031, -2037), and R-compounds had a small minus electrostatic potential (ESP) field in the cyclopentene-1,3-dione region. S-configured TX-2046 had weaker radiosensitizing activity than R-configured TX-2045, and TX-2046 had a small minus ESP field as well as R-configured TX-2043, -2030, - 2036. CONCLUSION: The cyclopentene-1,3-dione involved in the small minus ESP field affected the radiosensitizing activity of the TX-2036 series of molecules.
Assuntos
Desenho de Fármacos , Nitroimidazóis/química , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/química , Hipóxia Celular/efeitos dos fármacos , Ciclopentanos/síntese química , Ciclopentanos/química , Humanos , Nitroimidazóis/síntese química , Radiossensibilizantes/síntese química , Eletricidade Estática , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
BACKGROUND/AIM: Sugar molecules are often used as a tool to structurally modify chemical compounds. The features of synthesized sugar-conjugated TX-1877 derivatives were herein examined. MATERIALS AND METHODS: The molecular stabilities (reactivity) and hydrophobicities of sugar (e.g., monosaccharide and tetra-O-acetylated monosaccharide)-conjugated TXs were analyzed using a molecular simulation (e.g. molecular mechanics (MM) and molecular orbital (MO) analysis). RESULTS: The hydrophobicities of TX-1877 derivatives were increased by tetra-O-acetylation, and TX-2244 exhibited the most potent radiosensitizing activity (enhancement ratio: ER=2.30). CONCLUSION: The conformations and hydrophobicities of chemical compounds may be controlled by adding monosaccharide- and tetra-O-acetyl-conjugated sugars to TX-1877.
Assuntos
Desenho de Fármacos , Nitroimidazóis/química , Radiossensibilizantes/química , Relação Estrutura-Atividade , Animais , Linhagem Celular , Glicosilação , CamundongosRESUMO
BACKGROUND: To date, two cyclo-oxygenase (COX) isoforms, COX1 and COX2, have been identified. In the present study, the COX-inhibitory activities of TX-1123 derivatives with the 2-hydroxyarylidene-4-cyclopentene-1,3-dione structure were examined, and the binding profiles of TX-1123 to COXs were analyzed using docking simulations. MATERIALS AND METHODS: X-Ray data on COX1 [protein data bank (PDB) ID=1PGG] and COX2 (PDB ID=3LN1) were used for molecular interactive simulations. The interactive profiles of TX-1123 derivatives with COXs were examined using a molecular simulation technique with Molegro Virtual Docker (CLC bio, Aarhus, Denmark). RESULTS: TX-1123 exhibited COX1-inhibitory activity [half-maximal-inhibitory concentration (IC50)=1.57×10-5 M]. The COX2 inhibitory activity of TX-1123 was potent (IC50=1.16×10-6 M), and the ratio of COX1/COX2 inhibition was 13.5. TX-1123 bound to the COX2 molecule, and the oxygen atom of the 4-cyclopentene-1,3-dione region of TX-1123 interacted with Cys26 and Gln447 of COX2. CONCLUSION: The TX-1123-binding pocket of COX2 differs from that of the COX2-selective celecoxib-binding pocket. TX-1123 exhibited a different COX2-interactive mechanism from that of celecoxib.
Assuntos
Compostos de Benzilideno/farmacologia , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Ciclopentanos/farmacologia , Sítios de Ligação , Celecoxib/farmacologia , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 2/química , Cisteína/metabolismo , Glutamina/metabolismo , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Ligação ProteicaRESUMO
We have developed a self-assembled fluorescent cluster comprising a seminaphthorhodafluor (SNARF) derivative protected by a photoremovable o-nitrobenzyl group. Prior to UV irradiation, a colorless and nonfluorescent cluster was spontaneously assembled in aqueous solution. After UV irradiation, the self-assembled cluster remained intact and showed a large enhancement in pH-responsive fluorescence. The unique pH responsive fluorescent cluster could be used as a dual-emissive ratiometric fluorescent pH probe not only in the test tube but also in HeLa cell cultures.
RESUMO
Boron neutron capture therapy (BNCT) is one of the numbers of radiotherapies for treatment of certain cancers. The ability of low-dose irradiation with neutrons or radioactive beams to provide an acceptable quality of life is an objective which has not yet been achieved; therefore it will be necessary to increase the efficiency of the neutron capture reaction by lower dose irradiation and by achieving higher drug concentrations in living cells. Drug selectivity in targeting the affected cellular compartment is most important. Molecular design and synthesis of drugs should be based on high resolution structures and analysis of specific compounds and host molecules; however, it is necessary to obtain crystals for X-ray structural analysis. Because compounds containing bulky functional groups are difficult to crystalize due to their flexibility, the method described here makes it possible to stabilize these compounds by complexing them with protein molecules. We have first solved the three-dimensional structure of a BNCT drug-protein molecule combination at 1.26 Å resolution, and discuss the nature of the interaction between a BNCT drug and the protein molecule residues.
Assuntos
Compostos de Boro/química , Terapia por Captura de Nêutron de Boro , Muramidase/química , Quinoxalinas/química , Sítios de Ligação , Cristalização , Cristalografia por Raios X , Modelos Moleculares , Estrutura Molecular , Ligação ProteicaRESUMO
BACKGROUND: Protein tyrosine kinases (PTKs) play major roles in signal transduction during cell proliferation and apoptosis. Tyrphostin AG17 was previously shown to be a potent tumor growth inhibitor, while AG17 induced apoptosis and inhibited activity of cyclin-dependent kinase 2. We herein describe the binding features of tyrphostin AG17 analogs, such as TX-1123, with Src kinase (Src-K). MATERIALS AND METHODS: Structural data for Src-K were obtained from a protein data bank (ID=2SRC), and the molecular interactions between Src-K and TX-1123 derivatives were examined. RESULTS: TX-1123 exihibited potent Src-K inhibitory activity (half maximal-inhibitory concentration=2.2 µM), and fit into the pocket of the Src-K molecule as well as c-AMP did. CONCLUSION: The binding profiles of TX-1123 derivatives differed from each other, while their Src-K inhibitory activities were affected by their fit in the Src-K molecule.
Assuntos
Antineoplásicos/química , Compostos de Benzilideno/química , Ciclopentanos/química , Inibidores de Proteínas Quinases/química , Quinases da Família src/antagonistas & inibidores , Sítios de Ligação , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Ligação Proteica , Quinases da Família src/químicaRESUMO
The title compound, C25H31BF2N2O, is a potential boron tracedrug in boron neutron capture therapy (BNCT), in which the B atom adopts a distorted BN2F2 tetra-hedral geometry: it is soluble in dimethyl sulfoxide, di-methyl-formamide and methanol. The pyrrolyl-idene-methyl-pyrrole triple fused ring system is almost planar (r.m.s. deviation = 0.031â Å) and subtends a dihedral angle of 47.09â (5)° with the plane of the pendant phenol ring. The phenol -OH group is blocked from forming hydrogen bonds by the adjacent bulky tert-butyl groups. In the crystal, inversion dimers linked by pairs of very weak C-Hâ¯F inter-actions generate R 2 (2)(22) loops.
RESUMO
Prenyl residues confer divergent biological activities such as antipathogenic and antiherbivorous activities on phenolic compounds, including flavonoids, coumarins, and xanthones. To date, about 1,000 prenylated phenolics have been isolated, with these compounds containing various prenyl residues. However, all currently described plant prenyltransferases (PTs) have been shown specific for dimethylallyl diphosphate as the prenyl donor, while most of the complementary DNAs encoding these genes have been isolated from the Leguminosae. In this study, we describe the identification of a novel PT gene from lemon (Citrus limon), ClPT1, belonging to the homogentisate PT family. This gene encodes a PT that differs from other known PTs, including flavonoid-specific PTs, in polypeptide sequence. This membrane-bound enzyme was specific for geranyl diphosphate as the prenyl donor and coumarin as the prenyl acceptor. Moreover, the gene product was targeted to plastid in plant cells. To our knowledge, this is the novel aromatic PT specific to geranyl diphosphate from citrus species.
Assuntos
Citrus/enzimologia , Dimetilaliltranstransferase/metabolismo , Difosfatos/metabolismo , Diterpenos/metabolismo , Citrus/genética , Dimetilaliltranstransferase/genética , Dados de Sequência Molecular , Filogenia , Plantas Geneticamente Modificadas , Plastídeos/metabolismo , Ruta , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
BACKGROUND: Conventional therapies for diseases that are associated with protein aggregation typically prevent rather than clear protein aggregates. We have proposed neutron dynamic therapy (NDT) as a physical clearance therapy for protein aggregates. Advanced glycation end-products (AGEs), which are aggregated proteins, have been implicated in diabetes, Alzheimer's, and heart disease. Herein, we report the use of the boron tracedrug UTX-51, under thermal neutron irradiation, as an NDT for the targeted clearance of glycated bovine serum albumin (Gly-BSA), a model of AGEs. MATERIALS AND METHODS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed to detect Gly-BSA decomposition by thermal neutron irradiation treated with UTX-51. RESULTS: The combination of UTX-51 with neutron irradiation showed a decrease in band intensity of Gly-BSA. CONCLUSION: We present our NDT strategy, which has been used for the targeted clearance of Gly-BSA, suggesting that NDT with boron tracedrugs can be used for the treatment of AGEs-related disease.
Assuntos
Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro/métodos , Produtos Finais de Glicação Avançada/metabolismo , Soroalbumina Bovina/metabolismoRESUMO
BACKGROUND/AIM: We are developing a neutron dynamic therapy (NDT) with boron tracedrugs for a new mechanical-clearance treatment of pathotoxic misfolded, aggregated, and self-propagating prion-associated disease proteins. We present a compact neutron generator-based NDT using a boron tracedrug UTX-51. Our NDT is based on the weak thermal neutron-bombarded destructive action of UTX-51 on bovine serum albumin (BSA) using the neutron beams produced from a compact inertial electrostatic confinement fusion (IECF) neutron generator. RESULTS: BSA as an NDT molecular target was subjected to thermal neutron irradiation for eight hours using a compact neutron generator. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern showed no protein band when 2 nmoles of BSA were irradiated with more than 100 nmoles of UTX-51, while BSA was not affected when irradiated without UTX-51. CONCLUSION: For the first time, we have succeeded in the molecular destruction of a prion-disease model protein, BSA, by NDT with a boron tracedrug, UTX-51, using a compact neutron generator.
Assuntos
Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro/métodos , Nêutrons , Soroalbumina Bovina/efeitos da radiaçãoRESUMO
BACKGROUND: Recently, 5-aminolevulinic acid (5-ALA), precursors of protoporphyrin IX (PpIX), and Sn(IV) chlorin e6 (SnCe6) have been proposed as possible sonosensitizers for sonodynamic therapy of cancer. Therefore, we evaluated the pharmacokinetic properties and sonosensitizing activities of 5-ALA and SnCe6 in vivo by using the EMT6/KU tumor-bearing chick embryos. RESULTS: The concentration of PpIX in tumor and liver tissues and serum increased in a time-dependent manner after the i.v. administration of 5-ALA; PpIX concentrations reached their peak level after 5-7 h. The concentration of SnCe6 reached its maximum value in the tumor tissue and serum immediately after i.v. administration. The combined treatment of 5-ALA or SnCe6 with ultrasound irradiation showed a significant antitumor effect towards EMT6/KU solid tumors. CONCLUSION: We evaluated the pharmacokinetic properties and sonosensitizing activities of 5-ALA and SnCe6 in a chick embryo model and found that 5-ALA might be more suitable as a sonosensitizer than SnCe6.
Assuntos
Ácido Aminolevulínico/farmacologia , Metaloporfirinas/farmacologia , Neoplasias Experimentais/terapia , Terapia por Ultrassom , Ácido Aminolevulínico/farmacocinética , Animais , Linhagem Celular Tumoral , Embrião de Galinha , Metaloporfirinas/farmacocinética , Camundongos , Protoporfirinas/metabolismoRESUMO
BACKGROUND: Gc protein-derived macrophage-activating factor (GcMAF) occurs naturally in the human body. It has various functions, such as macrophage activation and antitumor activities. Recently, immunotherapy has become an attractive new strategy in the treatment of cancer. GcMAF-based immunotherapy can be combined with many other therapies. Sonodynamic therapy (SDT) using low-intensity ultrasound is a novel therapeutic modality. Ultrasound has been demonstrated to activate a number of sonosensitive agents allowing for the possibility of non-invasive targeted treatment for both superficial and deep-seated tumors. The current case study demonstrates that GcMAF and SDT can be used in combination with conventional therapies in patients with metastatic cancer, especially where treatment options are limited due to factors such as toxicity. This case study also suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT, to be used in combination with GcMAF immunotherapy as a systemic treatment.
Assuntos
Androstadienos/uso terapêutico , Neoplasias da Mama/terapia , Fatores Ativadores de Macrófagos/uso terapêutico , Terapia por Ultrassom/métodos , Proteína de Ligação a Vitamina D/uso terapêutico , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIM: The aims of this study were to evaluate the cell survival uncertainty distribution of radiation and to assess the accuracy of predictions of tumor response by using three different in vitro experimental cell cultures with radiosensitizers (including etanidazole). MATERIALS AND METHODS: Using EMT6 cells and X-rays, the cell survival fraction was obtained from 15, 34, and 21 different experiments under normoxic, hypoxic, and hypoxic-plus-radiosensitizer culture, respectively. RESULTS: The α coefficients were 0.257 ± 0.188, 0.078 ± 0.080, and 0.182 ± 0.116 Gy(-1), respectively. The ß coefficients were 0.0159 ± 0.0208, 0.0076 ± 0.0113, and 0.0062 ± 0.0077 Gy(-2), respectively. The α coefficient and the dose that killed half of the clonogens population (D50) were significantly different between normoxic cell and hypoxic cell cultures (p<0.01), respectively. The use of radiosensitizers under hypoxic conditions improved radiosensitivity. CONCLUSION: Our results suggest that parameter value distributions are required for biophysical modeling of applications for radiotherapy.
Assuntos
Neoplasias Mamárias Experimentais/radioterapia , Tolerância a Radiação , Animais , Fenômenos Biofísicos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Feminino , Neoplasias Mamárias Experimentais/patologia , Camundongos , Modelos Biológicos , IncertezaRESUMO
Antioxidants have been demonstrated to exert beneficial effects as pharmacotherapies for cardiovascular diseases. The in vitro systems generally employed to evaluate antioxidants, however, are limited by having no appreciable in vivo redox status of the antioxidants. Therefore, we used our developing chicken egg model to evaluate the in vivo antioxidative activity of a redox nanoparticle possessing 2,2,6,6-tetramethylpiperidine-1-oxyl (RNP(O)). The 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) elicited strong oxidative stress and its LD50 value for chick embryos was 3.5±0.9mg/egg. The low molecular weight nitroxide compound, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), which is known to have the highest level of antioxidant activity, showed no significant protective effect against AAPH-induced embryo lethality. On the contrary, RNP(O) had potent protective effects against AAPH-induced embryo lethality. Moreover, RNP(O) could significantly suppress the production of lipid peroxides in chick serum induced by hydrocortisone. Since RNP(O) has a longer retention time in blood than TEMPOL, RNP(O) may protect the embryo against lethal oxidative stress by suppressing lipid peroxidation. The validity of in vivo experiments using developing chicken eggs was supported by our data, where RNP(O) was determined to elicit strong antioxidative activity in vivo, irrespective of the lack of a significant difference in the in vitro activity between low-molecular weight TEMPOL and RNP(O). Our results support the use of the developing chicken egg model to evaluate the potential in vivo antioxidative activity of RNP(O).
Assuntos
Antioxidantes/farmacologia , Embrião de Galinha , Óxidos N-Cíclicos/farmacologia , Modelos Animais , Nanopartículas/administração & dosagem , Amidinas/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Hidrocortisona , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Oxidantes/toxicidade , Oxirredução , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
We describe our solution for removal of the low-density lipoprotein (LDL) depot contained in proteins and lipids as a 'druggable' target for atherosclerotic cardiovascular diseases by neutron dynamic therapy (NDT), which we developed using boron tracedrugs for NDT against bovine serum albumin as a model protein. Thus, we examined, among our developed boron tracedrugs, a boron-containing curcuminoid derivative UTX-51, to destroy freshly isolated human LDL dynamically under irradiated thermal neutron to obtain a decreased intensity of band of LDL treated with UTX-51 and thermal neutron irradiation in their SDS-PAGE and electrophoresis analysis. These results suggest that UTX-51 might be a novel candidate of 'beyond chemical' therapeutic agents for atherosclerotic cardiovascular disease.
Assuntos
Terapia por Captura de Nêutron de Boro/métodos , Boro/uso terapêutico , Lipoproteínas LDL/metabolismo , Nêutrons/uso terapêutico , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/radioterapia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/radioterapia , Bovinos , Humanos , Soroalbumina Bovina/metabolismoRESUMO
BACKGROUND: The group-specific component protein-derived macrophage-activating factor (GcMAF) has various biological activities, such as macrophage activation and antitumor activity. Clinical trials of GcMAF have been carried out for metastatic breast cancer, prostate cancer, and metastatic colorectal cancer. In this study, despite the complicated purification process of GcMAF, we used enzymatically-treated human serum containing GcMAF with a considerable macrophage-stimulating activity and antitumor activity. RESULTS: We detected GcMAF in degalactosylated/desialylated human serum by western blotting using an anti-human Gc globulin antibody, and Helix pomatia agglutinin lectin. We also found that GcMAF-containing human serum significantly enhanced the phagocytic activity of mouse peritoneal macrophages and extended the survival time of mice bearing Ehrlich ascites tumors. CONCLUSION: We demonstrated that GcMAF-containing human serum can be used as a potential macrophage activator for cancer immunotherapy.
Assuntos
Carcinoma de Ehrlich/prevenção & controle , Galactose/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Fatores Ativadores de Macrófagos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Soro/química , Ácidos Siálicos/metabolismo , Proteína de Ligação a Vitamina D/farmacologia , Animais , Western Blotting , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , Feminino , Humanos , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos ICRRESUMO
BACKGROUND: Group-specific component (Gc)-globulin-derived macrophage-activating factor (GcMAF) generated by a cascade of catalytic reactions with deglycosidase enzymes exerts antitumor activity. We hypothesized that degalactosyl Gc-globulin (DG3), a precursor of GcMAF, also plays a role in recovery from cancer as well as GcMAF due to progression of deglycosylation by generally resident sialidases and mannosidases. MATERIALS AND METHODS: We prepared the subtypes of DG3, such as 1f1f and 1s1s and its 22 homodimers, by using vitamin D3-binding Sepharose CL-6B and examined their antitumor activity in mice bearing Lewis lung carcinoma cells, by counting the number of nodules formed in their lungs. RESULTS: Antitumor activity of DG3 was observed regardless of its subtype, being equivalent to that of GcMAF. The injection route of DG3 affected its antitumor activity, with subcutaneous and intramuscular administration being more favorable than the intraperitoneal or intravenous route. In order to obtain significant antitumor activity, more than 160 ng/kg of DG3 were required. CONCLUSION: DG3 proved to be promising as an antitumor agent, similarly to GcMAF.
Assuntos
Carcinoma Pulmonar de Lewis/tratamento farmacológico , Galactose/metabolismo , Fatores Ativadores de Macrófagos/administração & dosagem , Proteína de Ligação a Vitamina D/administração & dosagem , Animais , Carcinoma Pulmonar de Lewis/metabolismo , Feminino , Humanos , Injeções Intramusculares , Injeções Intraperitoneais , Injeções Intravenosas , Injeções Subcutâneas , Fatores Ativadores de Macrófagos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Proteína de Ligação a Vitamina D/química , Proteína de Ligação a Vitamina D/farmacologiaRESUMO
BACKGROUND: Immunotherapy has become an attractive new strategy in the treatment of cancer. The laboratory and clinical study of cancer immunotherapy is rapidly advancing. However, in the clinical setting, the results of cancer immunotherapy are mixed. We therefore contend that cancer immunotherapy should be customized to each patient individually based on their immune status and propose an integrative immunotherapy approach with second-generation group-specific component macrophage activating factor (GcMAF)-containing human serum. PATIENTS AND METHODS: The standard protocol of our integrative cancer immunotherapy is as follows: i) 0.5 ml GcMAF-containing human serum is administered intramuscularly or subcutaneously once or twice per week for the duration of cancer therapy until all cancer cells are eradicated; ii) hyper T/natural killer (NK) cell therapy is given once per week for six weeks; iii) high-dose vitamin C is administered intravenously twice per week; iv) alpha lipoic acid (600 mg) is administered orally daily; v) vitamin D3 (5,000-10,000 IU) is administered orally daily. RESULTS: By March 2013, Saisei Mirai have treated over 345 patients with GcMAF. Among them we here present the cases of three patients for whom our integrative immunotherapy was remarkably effective. CONCLUSION: The results of our integrative immunotherapy seem hopeful. We also plan to conduct a comparative clinical study.>