Phenylacetylglutaminate (PG) and Phenylacetate (PN) are metabolites of Phenylbutyrate (PB) and are constituents of antineoplaston AS2-1. These are sodium salts of amino acid derivative and carboxylic acid that inhibit...Phenylacetylglutaminate (PG) and Phenylacetate (PN) are metabolites of Phenylbutyrate (PB) and are constituents of antineoplaston AS2-1. These are sodium salts of amino acid derivative and carboxylic acid that inhibit the growth of neoplastic cells without growth inhibitory effect in normal cells. The aim of this study was to identify molecular pathways involved in the anti-proliferative effect of antineoplastons. Using a total human genome microarray we have found that 1) Vitamin D3 upregulated protein (VDUP1) is significantly upregulated in response to PG and PN in the U87 glioblastoma cells;2) Isobologram analysis shows that PG and PN act in an additive or synergistic manner to effectively suppress proliferation of U87 cells;3) PG and PN cause cell cycle arrest, changes in expression of several cell cycle genes and suppress expression and activity of the G2/M checkpoint kinase, CHK1. The multiple cellular targets possibly make these compounds effective anti-proliferative agents. We propose that PG and PN in combination target important cellular pathways and upregulate VDUP1 leading to detachment-induced apoptosis in cancer cells.展开更多
The effects of differentiation inducer sodium phenylacetate on antigen expression of human breas cancer MDA-453 cells and their activity to induce allospecific cytotoxic T lymphocytes (CTL) in peripheral blood mononuc...The effects of differentiation inducer sodium phenylacetate on antigen expression of human breas cancer MDA-453 cells and their activity to induce allospecific cytotoxic T lymphocytes (CTL) in peripheral blood mononuclear cells (PBMC) were investigated. The results showed that sodium phenylacetate could the expression of HLA-A2 molecules, intercellular adhesion molecule-1 (ICAW-1) and protein HER-2/neu on the surface of MDA-453 cells. In mixed allogenic PBMC/MDA-453 cell (shared the same HLA-A2 locus) culture in vitro, MDA-453 cells could stimulate PBMC growth in the presence of low dose of interleukin-2 (IL-2 ), but sodium phenylacetate-treated MDA-453 cells were more potent for stimulating PBMC growth than the untreated cells. PBMC obtained from frow culture at 7th day could kill MDA-453 cells. The cytotoxicity of PBMC obtained form the culture at 21st day was restricted to MDA-453 cells (PBMC could hardly kill K562 and Raji cells), so the PBMC at this time could be called allospecific CTL. Sodium phenylacetate-treated MDA-453 cells were more potent for inducing allospecific CTL than the untreated cells in mixed allogenic PBMC/MDA-453 cell culture. In summary, sodium phenylacetate could increase the activity of breast cancer MDA-453 cells to induce allospecific CTL with a corresponding effect on antigen expression.展开更多
Esthesioneuroblastoma is a malignant tumor, arising in the upper nasal cavity, that could spread to the frontal lobe of the brain as well as metastasize to the lymph nodes. Due to the low incidence of this tumor, FDA-...Esthesioneuroblastoma is a malignant tumor, arising in the upper nasal cavity, that could spread to the frontal lobe of the brain as well as metastasize to the lymph nodes. Due to the low incidence of this tumor, FDA-approved treatment modalities do not exist and clinical trials have not been performed. We present an interesting case of a 66-year-old female, diagnosed with Kadish stage B esthesioneuroblastoma and stage IIA nonsmall cell carcinoma of the lung, who benefited from our treatment. Both malignancies were diagnosed in 2002 at which time the patient consented to undergo left upper lobectomy for her lung cancer, but she refused the craniofacial resection and radiation therapy recommended for treatment of her esthesioneuroblastoma. From 2003 to 2004 she received treatment at the Burzynski Clinic with oral sodium phenylbutyrate (0.2 g/kg/day). She tolerated the treatment very well without significant adverse events. Gradual reduction in her tumor size was confirmed by repeat MRIs. From treatment start in March 2003 to December 2003 her tumor decreased by 40%. Subsequent MRI from March 2004 revealed increased tumor size, which, however, was still a 13% reduction from the baseline MRI. What is important to mention is that in addition to shrinkage of the esthesioneuroblastoma, the patient obtained the clinical benefit of 3.5-years longer survival than was predicted for her lung cancer—whereas the median survival for a patient with stage IIA adenocarcinoma of the left upper lobe of the lung is approximately two years, our patient survived more than five and a half years. The effect of phenylbutyrate (PB) and its metabolite phenylacetate on neuroblastoma and lung cancer is documented by numerous preclinical studies and is also evident in this case. It is proposed that the activity of these two compounds is mediated through increased expression of the p21 tumor suppressor gene. p21 is a strong inhibitor of cyclin-D and cyclin-dependent kinase 4, which contribute to undifferentiated phenotype in neuroblastoma an展开更多
To study the effects of phenylacetate （PA） on cell proliferation and homeobox （HOX） genes expression in the colorectal carcinoma HCT-8 cell line, HCT-8 cells were grown in the presence or absence of PA. The cellul...To study the effects of phenylacetate （PA） on cell proliferation and homeobox （HOX） genes expression in the colorectal carcinoma HCT-8 cell line, HCT-8 cells were grown in the presence or absence of PA. The cellular proliferation inhibition was evaluated by the MTT assay. Twenty-two HOX genes were divided into three groups （ P1, P2, P3） according to their primer sequences, and the samples of cells were analyzed for the HOX genes＇ mRNA expression by means of the semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）. The level of the HOX genes＇ expression was expressed as the ratio expression rate of HOX gene to the β-actin. HCT-8 cells were treated with 1.0-5.0 mmol/L PA for 24-72 h. With the increase of the PA concentration or the prolongation of the treating time, the cell proliferation is inhibited in a dose- and time-dependent manner. The P1 group mRNA＊ expression（0. 5781 ±0. 0836） is significantly lower than that of the untreated group （0. 7701 ± 0. 0883 ） in HCT-8 cells （p 〈 0. 001 ）. Both the mRNA expressions of groups P2 （0. 3941 ± 0. 0819） and P3 （0. 5601 ± 0. 0736） in the PA treated group are significantly higher than those of the untreated groups P2（0. 1221±0. 0782） and P3 （0. 1806 ± 0. 0811 ） in HCT-8 cells（p 〈 0. 001）. PA could effectively inhibit cell proliferation by regulating the HOX genes expression and the mechanisms of the PA action are correlated with the transcription process in HCT-8 cells.展开更多
Objective: To improve the preparation of adherent lymphokine-activated killer (A-LAK) cells and study the synergistic anti-tumor effect of phenylacetate (PA) and A-LAK cells. Methods: A-LAK cells were obtained from pe...Objective: To improve the preparation of adherent lymphokine-activated killer (A-LAK) cells and study the synergistic anti-tumor effect of phenylacetate (PA) and A-LAK cells. Methods: A-LAK cells were obtained from peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) by using L-phenylalanine methyl ester (PME) to deplete immunosuppressive monocytes. The proliferation of SMMC7721 cell line treated with PA was studied. A-LAK cells were treated with the supernatant of SMMC7721 cells which had been pretreated with PA and the changes of the proliferation and anti-tumor activity of A-LAK cells were investigated. Results: The expansion of A-LAK cells was significantly higher than that of non-adherent LAK (NA-LAK) cells as well as regular LAK cells. The growth of SMMC7721 cells was significantly suppressed by PA. The supernatant of cultured tumor cells intensively suppressed the proliferation and cytotoxicity of A-LAK cells, but the suppressive effect of supernatant treated with PA previously was decreased. Conclusion: A-LAK cells could be simply prepared by using PME, and showed a synergistic anti-tumor effect with the combination of PA.展开更多
The crystal structure of Nd(ph-CH_2COO)_3H_2O has been determined by X-ray diffraction technique.The crystal behmgs to orthorhombic system with space group P_(na)2_1,cell parameters a=0.7983(1)nm, h=1.3957(1)nm,c=2.02...The crystal structure of Nd(ph-CH_2COO)_3H_2O has been determined by X-ray diffraction technique.The crystal behmgs to orthorhombic system with space group P_(na)2_1,cell parameters a=0.7983(1)nm, h=1.3957(1)nm,c=2.0282(2)nm;V=2.2598(15)nm^3,Z=4.The Mechanism and enthalpy changes of thermal decomposition reaction of the title complex have been studied by TG-DTG-DTA and DSC.展开更多
文摘Phenylacetylglutaminate (PG) and Phenylacetate (PN) are metabolites of Phenylbutyrate (PB) and are constituents of antineoplaston AS2-1. These are sodium salts of amino acid derivative and carboxylic acid that inhibit the growth of neoplastic cells without growth inhibitory effect in normal cells. The aim of this study was to identify molecular pathways involved in the anti-proliferative effect of antineoplastons. Using a total human genome microarray we have found that 1) Vitamin D3 upregulated protein (VDUP1) is significantly upregulated in response to PG and PN in the U87 glioblastoma cells;2) Isobologram analysis shows that PG and PN act in an additive or synergistic manner to effectively suppress proliferation of U87 cells;3) PG and PN cause cell cycle arrest, changes in expression of several cell cycle genes and suppress expression and activity of the G2/M checkpoint kinase, CHK1. The multiple cellular targets possibly make these compounds effective anti-proliferative agents. We propose that PG and PN in combination target important cellular pathways and upregulate VDUP1 leading to detachment-induced apoptosis in cancer cells.
文摘The effects of differentiation inducer sodium phenylacetate on antigen expression of human breas cancer MDA-453 cells and their activity to induce allospecific cytotoxic T lymphocytes (CTL) in peripheral blood mononuclear cells (PBMC) were investigated. The results showed that sodium phenylacetate could the expression of HLA-A2 molecules, intercellular adhesion molecule-1 (ICAW-1) and protein HER-2/neu on the surface of MDA-453 cells. In mixed allogenic PBMC/MDA-453 cell (shared the same HLA-A2 locus) culture in vitro, MDA-453 cells could stimulate PBMC growth in the presence of low dose of interleukin-2 (IL-2 ), but sodium phenylacetate-treated MDA-453 cells were more potent for stimulating PBMC growth than the untreated cells. PBMC obtained from frow culture at 7th day could kill MDA-453 cells. The cytotoxicity of PBMC obtained form the culture at 21st day was restricted to MDA-453 cells (PBMC could hardly kill K562 and Raji cells), so the PBMC at this time could be called allospecific CTL. Sodium phenylacetate-treated MDA-453 cells were more potent for inducing allospecific CTL than the untreated cells in mixed allogenic PBMC/MDA-453 cell culture. In summary, sodium phenylacetate could increase the activity of breast cancer MDA-453 cells to induce allospecific CTL with a corresponding effect on antigen expression.
文摘Esthesioneuroblastoma is a malignant tumor, arising in the upper nasal cavity, that could spread to the frontal lobe of the brain as well as metastasize to the lymph nodes. Due to the low incidence of this tumor, FDA-approved treatment modalities do not exist and clinical trials have not been performed. We present an interesting case of a 66-year-old female, diagnosed with Kadish stage B esthesioneuroblastoma and stage IIA nonsmall cell carcinoma of the lung, who benefited from our treatment. Both malignancies were diagnosed in 2002 at which time the patient consented to undergo left upper lobectomy for her lung cancer, but she refused the craniofacial resection and radiation therapy recommended for treatment of her esthesioneuroblastoma. From 2003 to 2004 she received treatment at the Burzynski Clinic with oral sodium phenylbutyrate (0.2 g/kg/day). She tolerated the treatment very well without significant adverse events. Gradual reduction in her tumor size was confirmed by repeat MRIs. From treatment start in March 2003 to December 2003 her tumor decreased by 40%. Subsequent MRI from March 2004 revealed increased tumor size, which, however, was still a 13% reduction from the baseline MRI. What is important to mention is that in addition to shrinkage of the esthesioneuroblastoma, the patient obtained the clinical benefit of 3.5-years longer survival than was predicted for her lung cancer—whereas the median survival for a patient with stage IIA adenocarcinoma of the left upper lobe of the lung is approximately two years, our patient survived more than five and a half years. The effect of phenylbutyrate (PB) and its metabolite phenylacetate on neuroblastoma and lung cancer is documented by numerous preclinical studies and is also evident in this case. It is proposed that the activity of these two compounds is mediated through increased expression of the p21 tumor suppressor gene. p21 is a strong inhibitor of cyclin-D and cyclin-dependent kinase 4, which contribute to undifferentiated phenotype in neuroblastoma an
文摘To study the effects of phenylacetate （PA） on cell proliferation and homeobox （HOX） genes expression in the colorectal carcinoma HCT-8 cell line, HCT-8 cells were grown in the presence or absence of PA. The cellular proliferation inhibition was evaluated by the MTT assay. Twenty-two HOX genes were divided into three groups （ P1, P2, P3） according to their primer sequences, and the samples of cells were analyzed for the HOX genes＇ mRNA expression by means of the semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）. The level of the HOX genes＇ expression was expressed as the ratio expression rate of HOX gene to the β-actin. HCT-8 cells were treated with 1.0-5.0 mmol/L PA for 24-72 h. With the increase of the PA concentration or the prolongation of the treating time, the cell proliferation is inhibited in a dose- and time-dependent manner. The P1 group mRNA＊ expression（0. 5781 ±0. 0836） is significantly lower than that of the untreated group （0. 7701 ± 0. 0883 ） in HCT-8 cells （p 〈 0. 001 ）. Both the mRNA expressions of groups P2 （0. 3941 ± 0. 0819） and P3 （0. 5601 ± 0. 0736） in the PA treated group are significantly higher than those of the untreated groups P2（0. 1221±0. 0782） and P3 （0. 1806 ± 0. 0811 ） in HCT-8 cells（p 〈 0. 001）. PA could effectively inhibit cell proliferation by regulating the HOX genes expression and the mechanisms of the PA action are correlated with the transcription process in HCT-8 cells.
基金This work was supported by a grant from the National 9th Five-Year Program of China (No. 96-906-01-20).
文摘Objective: To improve the preparation of adherent lymphokine-activated killer (A-LAK) cells and study the synergistic anti-tumor effect of phenylacetate (PA) and A-LAK cells. Methods: A-LAK cells were obtained from peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) by using L-phenylalanine methyl ester (PME) to deplete immunosuppressive monocytes. The proliferation of SMMC7721 cell line treated with PA was studied. A-LAK cells were treated with the supernatant of SMMC7721 cells which had been pretreated with PA and the changes of the proliferation and anti-tumor activity of A-LAK cells were investigated. Results: The expansion of A-LAK cells was significantly higher than that of non-adherent LAK (NA-LAK) cells as well as regular LAK cells. The growth of SMMC7721 cells was significantly suppressed by PA. The supernatant of cultured tumor cells intensively suppressed the proliferation and cytotoxicity of A-LAK cells, but the suppressive effect of supernatant treated with PA previously was decreased. Conclusion: A-LAK cells could be simply prepared by using PME, and showed a synergistic anti-tumor effect with the combination of PA.
文摘The crystal structure of Nd(ph-CH_2COO)_3H_2O has been determined by X-ray diffraction technique.The crystal behmgs to orthorhombic system with space group P_(na)2_1,cell parameters a=0.7983(1)nm, h=1.3957(1)nm,c=2.0282(2)nm;V=2.2598(15)nm^3,Z=4.The Mechanism and enthalpy changes of thermal decomposition reaction of the title complex have been studied by TG-DTG-DTA and DSC.
