Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies ar...Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies are needed for patients whose tumor recurs after first-line treatment. This single-arm, two-stage, interventional Phase II study evaluated the efficacy and safety of a combination of antineoplastons A10 and AS2-1. Nineteen patients were enrolled in the study (safety population), but fifteen patients with a median age of 9.4 years who met eligibility criteria were evaluated. The majority of subjects (12/15) were Caucasian and 8/15 (53%) were female. More than half (53%) of patients were diagnosed with glioblastoma and 33% with anaplastic astrocytoma. All patients had failed standard therapy including surgery, radiation, and chemotherapy. Antineoplastons were administered intravenously every four hours (median dose of A10 6.9 g/kg/d and AS2-1 0.30 g/kg/d) until objective response was documented and thereafter for a further 8 months. Clinical evaluations were performed every 8 weeks. All patients enrolled in the study were included in the safety analysis but only patients fulfilling the inclusion criteria were included in the efficacy evaluation. The duration of treatment with antineoplastons ranged from 2 weeks to 120 weeks. A complete response was documented in 2/15 (13%), partial response in 2/15 (13%), stable disease in 3/15 (20%). Progression-free survival at six months was 47% and overall survival (OS) at one year was 33.3%. One patient (6.7%) survived 10 years from treatment start. A small group of patients suffered reversible Grade 3 and 4 toxicities including hypernatremia 2/19 (11%) and decrease of neutrophils 1/19 (5%). There were no chronic toxicities. There was improvement of quality of life in patients who had objective response. It is concluded that antineoplastons show efficacy with an acceptable profile in this cohort of patients with recurrent high-grade glioma.展开更多
Background:Cancerous ascites is a common and severe complication that occurs in patients with late-stage malignant tumors.The prognosis of cancerous ascites is poor,clinical treatment is difficult and therapeutic outc...Background:Cancerous ascites is a common and severe complication that occurs in patients with late-stage malignant tumors.The prognosis of cancerous ascites is poor,clinical treatment is difficult and therapeutic outcome is disappointing.In the present study,tumor cell-derived vesicles were used as drug delivery vehicles that encapsulated a chemotherapeutic agent and were perfused into a patients’abdominal cavity to effectively kill the cancer cells in cancerous ascites.Pre-clinical data has demonstrated that tumor vesicles that carry low-dose chemotherapeutics can efficiently eliminate metastatic tumor cells in the abdominal cavity with minimal toxic or adverse effects.When combined,tumor cell-derived vesicles can sensitize tumor cells,which facilitates the entry of chemotherapeutics into tumor cells,thereby enhancing killing of tumor cells and limiting the risk of drug resistance.In this study,we designed a clinical trial to evaluate the safety and efficacy of intraperitoneal perfusion with tumor vesicle-encapsulated methotrexate for the treatment of cancerous ascites.Methods:Sixty patients with cancerous ascites were enrolled in this open,randomized and controlled clinical trial.Participants were randomly assigned a visit number and,according to their visiting order for which a random numerical table was used,were assigned to the trial group or the control group in a 1:1 ratio.The change in ascetic volume was used as the study outcome and adverse events were monitored during the entire length of the study.Conclusion:In this clinical trial,randomization and electronic case report forms were implemented.The trial indicated that tumor vesicle-encapsulated methotrexate was proposed to be a safe and effective method for treating malignant ascites.Our study may provide at the first time evidence for the clinical application of tumor vesicles in tumor therapy.展开更多
The detection of very high energy γ-ray emission from the Galactic center has been reported by four independent groups. One of these γ-ray sources, the 10 TeV -γ-ray radiation reported by HESS, has been suggested a...The detection of very high energy γ-ray emission from the Galactic center has been reported by four independent groups. One of these γ-ray sources, the 10 TeV -γ-ray radiation reported by HESS, has been suggested as having a hadronic origin when relativistic protons are injected into and interact with the dense ambient gas. Assuming that such relativistic protons required by the hadronic model come from the tidal disruption of a star by the massive black hole of Sgr A＊, we explore the spectrum of the relativis- tic protons. In the calculations, we investigate cases where different types of stars are tidally disrupted by the black hole of Sgr A＊, and we consider that different diffusion mechanisms are used for the propagation of protons. The initial energy distribution of the injected spectrum of protons is assumed to follow a power-law with an exponential cut-off, and we derive the different indices of the injected spectra for the tidal disruption of different types of stars. For the best fit to the spectrum of photons detected by HESS, the spectral index of the injected relativistic protons is about 2.05 when a red giant is tidally disrupted by the black hole of Sgr A＊ and the diffusion mechanism is the Effective Confinement of Protons.展开更多
By means of programs GTMPAC based- on generalized triangle method,analysis and synthesis of mechanism design in accordance with absolutely graphicalmethod( absolutely germetrical method) are developed.In this paper,we...By means of programs GTMPAC based- on generalized triangle method,analysis and synthesis of mechanism design in accordance with absolutely graphicalmethod( absolutely germetrical method) are developed.In this paper,we make aspecial study about centering- point curve and circling- point curve and couplercurves based on Ball’s points.展开更多
文摘Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies are needed for patients whose tumor recurs after first-line treatment. This single-arm, two-stage, interventional Phase II study evaluated the efficacy and safety of a combination of antineoplastons A10 and AS2-1. Nineteen patients were enrolled in the study (safety population), but fifteen patients with a median age of 9.4 years who met eligibility criteria were evaluated. The majority of subjects (12/15) were Caucasian and 8/15 (53%) were female. More than half (53%) of patients were diagnosed with glioblastoma and 33% with anaplastic astrocytoma. All patients had failed standard therapy including surgery, radiation, and chemotherapy. Antineoplastons were administered intravenously every four hours (median dose of A10 6.9 g/kg/d and AS2-1 0.30 g/kg/d) until objective response was documented and thereafter for a further 8 months. Clinical evaluations were performed every 8 weeks. All patients enrolled in the study were included in the safety analysis but only patients fulfilling the inclusion criteria were included in the efficacy evaluation. The duration of treatment with antineoplastons ranged from 2 weeks to 120 weeks. A complete response was documented in 2/15 (13%), partial response in 2/15 (13%), stable disease in 3/15 (20%). Progression-free survival at six months was 47% and overall survival (OS) at one year was 33.3%. One patient (6.7%) survived 10 years from treatment start. A small group of patients suffered reversible Grade 3 and 4 toxicities including hypernatremia 2/19 (11%) and decrease of neutrophils 1/19 (5%). There were no chronic toxicities. There was improvement of quality of life in patients who had objective response. It is concluded that antineoplastons show efficacy with an acceptable profile in this cohort of patients with recurrent high-grade glioma.
文摘Background:Cancerous ascites is a common and severe complication that occurs in patients with late-stage malignant tumors.The prognosis of cancerous ascites is poor,clinical treatment is difficult and therapeutic outcome is disappointing.In the present study,tumor cell-derived vesicles were used as drug delivery vehicles that encapsulated a chemotherapeutic agent and were perfused into a patients’abdominal cavity to effectively kill the cancer cells in cancerous ascites.Pre-clinical data has demonstrated that tumor vesicles that carry low-dose chemotherapeutics can efficiently eliminate metastatic tumor cells in the abdominal cavity with minimal toxic or adverse effects.When combined,tumor cell-derived vesicles can sensitize tumor cells,which facilitates the entry of chemotherapeutics into tumor cells,thereby enhancing killing of tumor cells and limiting the risk of drug resistance.In this study,we designed a clinical trial to evaluate the safety and efficacy of intraperitoneal perfusion with tumor vesicle-encapsulated methotrexate for the treatment of cancerous ascites.Methods:Sixty patients with cancerous ascites were enrolled in this open,randomized and controlled clinical trial.Participants were randomly assigned a visit number and,according to their visiting order for which a random numerical table was used,were assigned to the trial group or the control group in a 1:1 ratio.The change in ascetic volume was used as the study outcome and adverse events were monitored during the entire length of the study.Conclusion:In this clinical trial,randomization and electronic case report forms were implemented.The trial indicated that tumor vesicle-encapsulated methotrexate was proposed to be a safe and effective method for treating malignant ascites.Our study may provide at the first time evidence for the clinical application of tumor vesicles in tumor therapy.
基金funded by the National Natural Science Foundation of China (Grant Nos. 10873015, 10778716, 10573021, 10778064, 10673001 and 10433010)the National Basic Research Program of China (Grant 2009CB824800)
文摘The detection of very high energy γ-ray emission from the Galactic center has been reported by four independent groups. One of these γ-ray sources, the 10 TeV -γ-ray radiation reported by HESS, has been suggested as having a hadronic origin when relativistic protons are injected into and interact with the dense ambient gas. Assuming that such relativistic protons required by the hadronic model come from the tidal disruption of a star by the massive black hole of Sgr A＊, we explore the spectrum of the relativis- tic protons. In the calculations, we investigate cases where different types of stars are tidally disrupted by the black hole of Sgr A＊, and we consider that different diffusion mechanisms are used for the propagation of protons. The initial energy distribution of the injected spectrum of protons is assumed to follow a power-law with an exponential cut-off, and we derive the different indices of the injected spectra for the tidal disruption of different types of stars. For the best fit to the spectrum of photons detected by HESS, the spectral index of the injected relativistic protons is about 2.05 when a red giant is tidally disrupted by the black hole of Sgr A＊ and the diffusion mechanism is the Effective Confinement of Protons.
文摘By means of programs GTMPAC based- on generalized triangle method,analysis and synthesis of mechanism design in accordance with absolutely graphicalmethod( absolutely germetrical method) are developed.In this paper,we make aspecial study about centering- point curve and circling- point curve and couplercurves based on Ball’s points.
