US20210236860A1 - Selective removal of cells having accumulated agents - Google Patents
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- US20210236860A1 US20210236860A1 US17/177,140 US202117177140A US2021236860A1 US 20210236860 A1 US20210236860 A1 US 20210236860A1 US 202117177140 A US202117177140 A US 202117177140A US 2021236860 A1 US2021236860 A1 US 2021236860A1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N13/00—Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0081—Purging biological preparations of unwanted cells
- C12N5/0093—Purging against cancer cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/32—Surgical cutting instruments
- A61B17/320068—Surgical cutting instruments using mechanical vibrations, e.g. ultrasonic
- A61B2017/320069—Surgical cutting instruments using mechanical vibrations, e.g. ultrasonic for ablating tissue
Definitions
- nucleolin a protein normally expressed in the nucleus or the cytoplasm has been shown to be expressed at the cell surface in neoplastic cells and endothelial cells of angiogenic vessels in vivo.
- Mi Y, et al. Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin. J Biol Chem 278:8572-9 (2003); Sven C, et al. Nucleolin Expressed at the Cell Surface is a Marker of Endothelial Cells in Angiogenic Blood Vessels, Journal of Cell Biology , Vol.
- P-gp P-glycoprotein
- MDR multidrug resistance
- Intracellular lipids accumulation is commonly observed in advanced atherosclerotic plaques. Monocyte infiltration in the intima layer of the vascular wall is followed by differentiation into macrophages, which in turn take up modified lipoproteins and become macrophage foam cells as a result of such intracellular lipids accumulation. Persson J, et al. Interleukin-1 beta and tumour necrosis factor-alpha impede neutral lipid turnover in macrophage-derived foam cells, BMC Immunology, 9(7) (2008). Obesity is associate with the accumulation of lipids in fat cells.
- M. tubercolosis causes the formation of hard nodules or tubercles in the lungs, parasitizes macrophages by blocking the phagosome-lysosome fusion, a process called phagosome maturation arrest, and by replicating inside the phagosome. Vergne I, et al. Cell Biology of Mycobacterium tubercolosis Phagosome, Ann Rev Cell Dev Biol ., Vol. 20, 367-94 (2004). Similarly, P.
- aeruginosa colonizes the lungs of patients with cystic fibrosis and produces biofilms, alginates, and specific lipid A modifications, which allow the bacteria to escape immune response and cause severe chronic inflammation.
- Moskowitz S M et al. The Role of Pseudomonas Lipopolysaccharide in Cystic Fibrosis Airway Infection, Subcell Biochem ., Vol. 53, 241-53 (2010). Production of biofilms by Haemophilus influenzae, Streptococcus pneumoniae , and other bacteria, has been linked to chronic otitis media in pediatric patients.
- Hall-Stoodley L et al. Direct Detection of Bacterial Biofilms on the Middle-Ear Mucosa of Children With Chronic Otitis Media, JAMA , Vol. 256, No. 2, 202-11 (2006).
- Plasmodium the agent causing malaria, replicates and accumulates inside erythrocytes, provoking cell rupture and dissemination of the agent, while the main sites of sequestration of the infected erythrocytes containing the trophozoites, schizonts and gametocytes of the parasite have been shown to be the lung, spleen, and adipose tissue, but also the brain, skin, bone marrow, and skeletal and cardiac muscle.
- Franke-Fayard B et al.
- Viruses replicate in the host cell, and the accumulation of the viral particles may result in changes to the plasma membrane. Examples include HIV, hepatitis C and rhinovirus. Ma Y, et al. NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly, J Virol. 82 (15) 7624-39 (2008); Korant B D, Butterworth B E, Inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides, J Virol. 18(1):298-306 (1976).
- Ultrasound is a technique that may be used to destroy or induce apoptosis of cells.
- the ultrasound is targeted to harmonic frequencies of the cross-linked cell membranes or components.
- the present invention is a method of treating a condition associate with accumulation of an agent in cells in a patient comprising exposing the cells to ultrasound, to selectively kill or induce apoptosis in the cells.
- the cells include the accumulated agent.
- the present invention is a method of removing cells from a sample, comprising exposing the sample to ultrasound, to selectively kill or induce apoptosis in the cells.
- the cells comprise an accumulated agent.
- the present invention makes use of the discovery that the differential resonant frequency of a cell caused by the accumulation of at least one agent that causes, or is associated with, a pathological or undesired condition, such as proteins, lipids, bacteria, viruses, parasites or particles, may be used to distinguish and eliminate cells in which the accumulated agent leads to a difference in the resonant frequency of the cell, by applying ultrasound treatment.
- the cells associated with the accumulated agent have a resonant frequency which is distinct from cells of the same type.
- the cells with the accumulated agent will be destroyed or induced to undergo apoptosis.
- the cells are not AGE-modified cells.
- the cells are not tumor cells.
- the cells are not cancerous.
- the ultrasound technique for removing cell-associated accumulation from a patient is selected for its ability to selectively kill or induce apoptosis in cells having accumulation of the agent associated with the pathological condition, while avoiding removal or destruction of cells that do not present the accumulation.
- cells expressing high levels of nucleolin on the plasma membrane of the cell may be selected due changes in the stiffness and deformability of the cell.
- “selectively kill or induce apoptosis” means that more of the cells which are the target of the killing or inducing apoptosis are so affected, as compared to other cell subject to the same exposure.
- Ultrasound devices can be used according to practices well known to those skilled in the art to destroy cells by vibrational techniques, for example U.S. Pat. No. 5,601,526 (1997) and International Publication No. WO2009/143411 (2009).
- Ultrasound parameters such as frequency, power and pulsation, can be screened for effectiveness in selectively destroying the targeted cells. Differential destruction or inducement of apoptosis may be by selection of the stiffer cells, or by selection of the cells by their resonant frequencies.
- Ultrasound as described above can be applied to a subject with monitoring to determine that inflammatory responses such as fever or swelling do not exceed limits well known to be safe. This process can be repeated at intervals to maintain a level of therapeutic benefit.
- Evaluation of improvement or maintenance of a desired result can be used to direct the frequency of reapplication of ultrasound according to the present invention.
- the application and reapplication can be determined with the goal of gradual improvement to avoid overwhelming natural mechanisms, such as removal of cells and cellular debris by scavenging cells.
- a variety of techniques are available to determine whether ultrasound may be used to selectively remove or kill the cells having the accumulated agent, that leads to, or is associated with, a pathological or undesired condition.
- the stiffness of individual cells may be determined, by techniques such as those described in U.S. Pat. No. 6,067,859 (2000).
- Elastic properties of tissue may be measured, by techniques such as those described in U.S. Pat. No. 7,751,057 (2010).
- application of a variety of ultrasound parameters to cells or a tissue sample, followed by examination of the cells or the tissue sample for destruction or subsequent apoptosis may also be used to determine whether ultrasound may selectively remove or kill the cells.
- Blood of a patient containing leukemia cells expressing nucleolin on the cell surface is treated with ultrasound.
- a blood sample is taken for further analysis.
- Leukemia cells are isolated from the blood sample, and examined using an optical stretcher (U.S. Pat. No. 6,067,859), to determine the relative stiffness of the cells and/or the resonant vibrational frequencies of the cell. This information is then used to select driving frequencies, intensity and length of time of treatment of the ultrasound, to selectively destroy or induce apoptosis, in the leukemia cells in vivo or ex vivo.
- Colon tissue from a patient containing colon cancer cells that present a multidrug resistance (MDR) phenotype are examined and determined to be overexpressing P-glycoprotein on the cell surface.
- the cells are then examined using an optical stretcher (U.S. Pat. No. 6,067,859), to determine the relative stiffness of the cells and/or the resonant vibrational frequencies of the cell. This information is then used to select driving frequencies, intensity and length of time of treatment of the ultrasound.
- an ultrasound generating probe may be included at the tip of a colonoscopy device.
- the ultrasound generating probe could generate pulses of ultrasound at the appropriate frequency, to selectively destroy colon cancer cells that present a multidrug resistance (MDR) phenotype, after the probe has been placed proximate to the tumor. The success of the treatment is monitored by subsequent colonoscopy.
- MDR multidrug resistance
- Blood of a patient, containing erythrocytes infected with Plasmodium is treated with ultrasound.
- a blood sample is taken for further analysis.
- Erythrocytes infected with Plasmodium are isolated from the blood sample, and examined using an optical stretcher (U.S. Pat. No. 6,067,859), to determine the relative stiffness of the erythrocytes and/or the resonant vibrational frequencies of the erythrocytes.
- the Plasmodium parasite could also be examined using the optical stretcher, to determine ultrasound parameters capable of direct destruction of the parasite. This information is then used to select driving frequencies, intensity and length of time of treatment of the ultrasound, to selectively destroy infected erythrocytes and/or the Plasmodium parasites, in the patient's blood either in vivo or ex vivo.
- a biopsy of an area in the lung of a patient containing tubercles and macrophages infected with M. tubercolosis is taken.
- the biopsy is treated with ultrasound applied at a range of frequencies and intensities, to determine conditions necessary to selectively destroy or induce apoptosis in the infected marcophages, the tubercles and/or the M. tubercolosis bacterial cells.
- the lungs of the patient are then treated with ultrasound. Time of exposure may range from three to sixty minutes daily for up to 20 days. At the end of the treatment, the patients are tested to determine the reduction in the size and/or number of tubercles present in the lungs of the patient.
- An alginate sample from the lungs of the patient is treated with ultrasound applied at a range of frequencies and intensities, to determine conditions necessary to selectively destroy or break down the alginate.
- the lungs of the patient are then treated with ultrasound.
- Time of exposure may range from three to sixty minutes daily for up to 20 days.
- the patient is tested to determine the reduction of alginates in the lungs.
Abstract
A method of treating a condition associate with accumulation of an agent in cells in a patient includes exposing the cells to ultrasound, to selectively kill or induce apoptosis in the cells. The cells include the accumulated agent.
Description
- Accumulation of agents, such as proteins, lipids, bacteria, viruses, parasites or particles, leads to, or is associated with, pathological conditions. For example, nucleolin, a protein normally expressed in the nucleus or the cytoplasm has been shown to be expressed at the cell surface in neoplastic cells and endothelial cells of angiogenic vessels in vivo. Mi Y, et al. Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin. J Biol Chem 278:8572-9 (2003); Sven C, et al. Nucleolin Expressed at the Cell Surface is a Marker of Endothelial Cells in Angiogenic Blood Vessels, Journal of Cell Biology, Vol. 164, No. 4, 871-878 (2003). Another example is P-glycoprotein (P-gp), a plasma membrane protein, which is over expressed in tumor cells that present a multidrug resistance (MDR) phenotype, which causes efflux of several structurally unrelated therapeutic drugs used for cancer treatment. Loo T W, et al. Identification of Residues in the Drug Translocation Pathway of the Human Multidrug Resistance P-glycoprotein by Arginine Mutagenesis, Journal of Biological Chemistry, Vol. 284, No. 36, 24074-24087 (2009). Deposition and subsequent accumulation of intracellular protein aggregates has been observed in several neurodegenerative disorders, such as a-synuclein in Parkinson's disease, β-amyloid and tau in Alzheimer's disease, and huntingtin in Huntington's diseases, and prion protein (PrP) in transmissible prion encephalopathies. Brandin P, et al. Prion-Like Transmission of Protein Aggregates in Neurodegenerative Diseases, Nat Rev Mol Cell Biol. Vol. 11, No. 4, 301-307 (2010). Poly A binding protein (PABP) accumulates in the cytoplasm of beta herpesviruses (HCMV)-infected cells. Perez C, et al. Translational control of cytoplasmic poly A binding protein (PABP) abundance in HCMV-infected cells, J Virol. Oct. 27, 2010 Epub.
- Intracellular lipids accumulation is commonly observed in advanced atherosclerotic plaques. Monocyte infiltration in the intima layer of the vascular wall is followed by differentiation into macrophages, which in turn take up modified lipoproteins and become macrophage foam cells as a result of such intracellular lipids accumulation. Persson J, et al. Interleukin-1 beta and tumour necrosis factor-alpha impede neutral lipid turnover in macrophage-derived foam cells, BMC Immunology, 9(7) (2008). Obesity is associate with the accumulation of lipids in fat cells.
- Some bacteria may accumulate inside cells, for example Mycobacterium tubercolosis and Pseudomonas aeruginosa. M. tubercolosis causes the formation of hard nodules or tubercles in the lungs, parasitizes macrophages by blocking the phagosome-lysosome fusion, a process called phagosome maturation arrest, and by replicating inside the phagosome. Vergne I, et al. Cell Biology of Mycobacterium tubercolosis Phagosome, Ann Rev Cell Dev Biol., Vol. 20, 367-94 (2004). Similarly, P. aeruginosa colonizes the lungs of patients with cystic fibrosis and produces biofilms, alginates, and specific lipid A modifications, which allow the bacteria to escape immune response and cause severe chronic inflammation. Moskowitz S M, et al. The Role of Pseudomonas Lipopolysaccharide in Cystic Fibrosis Airway Infection, Subcell Biochem., Vol. 53, 241-53 (2010). Production of biofilms by Haemophilus influenzae, Streptococcus pneumoniae, and other bacteria, has been linked to chronic otitis media in pediatric patients. Hall-Stoodley L, et al. Direct Detection of Bacterial Biofilms on the Middle-Ear Mucosa of Children With Chronic Otitis Media, JAMA, Vol. 256, No. 2, 202-11 (2006).
- Some protozoan parasites present intracellular accumulation, for example Plasmodium, Leishmania, Trypanosoma and Toxoplasma. Plasmodium, the agent causing malaria, replicates and accumulates inside erythrocytes, provoking cell rupture and dissemination of the agent, while the main sites of sequestration of the infected erythrocytes containing the trophozoites, schizonts and gametocytes of the parasite have been shown to be the lung, spleen, and adipose tissue, but also the brain, skin, bone marrow, and skeletal and cardiac muscle. Franke-Fayard B, et al. Sequestration and Tissue Accumulation of Human Malaria Parasites: Can We Learn Anything from Rodent Models of Malaria?, PLoS Pathogens, Vol. 6, No. 9, e1001032 (2010). Similarly, Leishmania mexicana and Trypanosome cruzi reside and proliferate inside macrophages. Zhang S et al. Delineation of Diverse Macrophage Activation Programs in Response to Intracellular Parasites and Cytokines, PLoS Negl Trop Dis, Vol. 4, No. 3: e648 (2010).
- Viruses replicate in the host cell, and the accumulation of the viral particles may result in changes to the plasma membrane. Examples include HIV, hepatitis C and rhinovirus. Ma Y, et al. NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly, J Virol. 82 (15) 7624-39 (2008); Korant B D, Butterworth B E, Inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides, J Virol. 18(1):298-306 (1976).
- Ultrasound is a technique that may be used to destroy or induce apoptosis of cells. U.S. Pat. No. 6,821,274 (2004). The technique has been used to selectively remove or kill cells based on differences is the membrane stiffness, such as that caused by cross-linking from AGE-modification. The ultrasound is targeted to harmonic frequencies of the cross-linked cell membranes or components. International Publication No. WO2009/143411 (2009).
- In a first aspect, the present invention is a method of treating a condition associate with accumulation of an agent in cells in a patient comprising exposing the cells to ultrasound, to selectively kill or induce apoptosis in the cells. The cells include the accumulated agent.
- In a second aspect, the present invention is a method of removing cells from a sample, comprising exposing the sample to ultrasound, to selectively kill or induce apoptosis in the cells. The cells comprise an accumulated agent.
- The present invention makes use of the discovery that the differential resonant frequency of a cell caused by the accumulation of at least one agent that causes, or is associated with, a pathological or undesired condition, such as proteins, lipids, bacteria, viruses, parasites or particles, may be used to distinguish and eliminate cells in which the accumulated agent leads to a difference in the resonant frequency of the cell, by applying ultrasound treatment. The cells associated with the accumulated agent have a resonant frequency which is distinct from cells of the same type. By selecting the frequency of the ultrasound applied to the tissue to feed energy into the resonant frequency, the cells with the accumulated agent will be destroyed or induced to undergo apoptosis. In an aspect of the invention, the cells are not AGE-modified cells. In another aspect of the invention, the cells are not tumor cells. In yet another aspect of the invention, the cells are not cancerous.
- The ultrasound technique for removing cell-associated accumulation from a patient is selected for its ability to selectively kill or induce apoptosis in cells having accumulation of the agent associated with the pathological condition, while avoiding removal or destruction of cells that do not present the accumulation. For example, cells expressing high levels of nucleolin on the plasma membrane of the cell may be selected due changes in the stiffness and deformability of the cell. As used herein, “selectively kill or induce apoptosis” means that more of the cells which are the target of the killing or inducing apoptosis are so affected, as compared to other cell subject to the same exposure.
- Ultrasound devices can be used according to practices well known to those skilled in the art to destroy cells by vibrational techniques, for example U.S. Pat. No. 5,601,526 (1997) and International Publication No. WO2009/143411 (2009). Ultrasound parameters, such as frequency, power and pulsation, can be screened for effectiveness in selectively destroying the targeted cells. Differential destruction or inducement of apoptosis may be by selection of the stiffer cells, or by selection of the cells by their resonant frequencies. Ultrasound as described above can be applied to a subject with monitoring to determine that inflammatory responses such as fever or swelling do not exceed limits well known to be safe. This process can be repeated at intervals to maintain a level of therapeutic benefit. Evaluation of improvement or maintenance of a desired result can be used to direct the frequency of reapplication of ultrasound according to the present invention. The application and reapplication can be determined with the goal of gradual improvement to avoid overwhelming natural mechanisms, such as removal of cells and cellular debris by scavenging cells.
- A variety of techniques are available to determine whether ultrasound may be used to selectively remove or kill the cells having the accumulated agent, that leads to, or is associated with, a pathological or undesired condition. The stiffness of individual cells may be determined, by techniques such as those described in U.S. Pat. No. 6,067,859 (2000). Elastic properties of tissue may be measured, by techniques such as those described in U.S. Pat. No. 7,751,057 (2010). Furthermore, application of a variety of ultrasound parameters to cells or a tissue sample, followed by examination of the cells or the tissue sample for destruction or subsequent apoptosis, may also be used to determine whether ultrasound may selectively remove or kill the cells.
- Blood of a patient containing leukemia cells expressing nucleolin on the cell surface is treated with ultrasound. After first diagnosing the patient, a blood sample is taken for further analysis. Leukemia cells are isolated from the blood sample, and examined using an optical stretcher (U.S. Pat. No. 6,067,859), to determine the relative stiffness of the cells and/or the resonant vibrational frequencies of the cell. This information is then used to select driving frequencies, intensity and length of time of treatment of the ultrasound, to selectively destroy or induce apoptosis, in the leukemia cells in vivo or ex vivo.
- Colon tissue from a patient containing colon cancer cells that present a multidrug resistance (MDR) phenotype are examined and determined to be overexpressing P-glycoprotein on the cell surface. The cells are then examined using an optical stretcher (U.S. Pat. No. 6,067,859), to determine the relative stiffness of the cells and/or the resonant vibrational frequencies of the cell. This information is then used to select driving frequencies, intensity and length of time of treatment of the ultrasound. For example, an ultrasound generating probe may be included at the tip of a colonoscopy device. The ultrasound generating probe could generate pulses of ultrasound at the appropriate frequency, to selectively destroy colon cancer cells that present a multidrug resistance (MDR) phenotype, after the probe has been placed proximate to the tumor. The success of the treatment is monitored by subsequent colonoscopy.
- Blood of a patient, containing erythrocytes infected with Plasmodium, is treated with ultrasound. After first diagnosing the patient, a blood sample is taken for further analysis. Erythrocytes infected with Plasmodium are isolated from the blood sample, and examined using an optical stretcher (U.S. Pat. No. 6,067,859), to determine the relative stiffness of the erythrocytes and/or the resonant vibrational frequencies of the erythrocytes. In addition, the Plasmodium parasite could also be examined using the optical stretcher, to determine ultrasound parameters capable of direct destruction of the parasite. This information is then used to select driving frequencies, intensity and length of time of treatment of the ultrasound, to selectively destroy infected erythrocytes and/or the Plasmodium parasites, in the patient's blood either in vivo or ex vivo.
- A biopsy of an area in the lung of a patient containing tubercles and macrophages infected with M. tubercolosis is taken. The biopsy is treated with ultrasound applied at a range of frequencies and intensities, to determine conditions necessary to selectively destroy or induce apoptosis in the infected marcophages, the tubercles and/or the M. tubercolosis bacterial cells. The lungs of the patient are then treated with ultrasound. Time of exposure may range from three to sixty minutes daily for up to 20 days. At the end of the treatment, the patients are tested to determine the reduction in the size and/or number of tubercles present in the lungs of the patient.
- An alginate sample from the lungs of the patient is treated with ultrasound applied at a range of frequencies and intensities, to determine conditions necessary to selectively destroy or break down the alginate. The lungs of the patient are then treated with ultrasound. Time of exposure may range from three to sixty minutes daily for up to 20 days. At the end of the treatment, the patient is tested to determine the reduction of alginates in the lungs.
- 1. Mi Y, et al. Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin. J Biol Chem 278:8572-9 (2003).
- 2. Sven C, et al, Nucleolin Expressed at the Cell Surface is a Marker of Endothelial Cells in Angiogenic Blood Vessels, Journal of Cell Biology, Vol. 164, No. 4, 871-878 (2003).
- 3. Loo T W, et al. Identification of Residues in the Drug Translocation Pathway of the Human Multidrug Resistance P-glycoprotein by Arginine Mutagenesis, Journal of Biological Chemistry, Vol. 284, No. 36, 24074-24087 (2009).
- 4. Brandin P, et al. Prion-Like Transmission of Protein Aggregates in Neurodegenerative Diseases, Nat Rev Mol Cell Biol. Vol. 11, No. 4, 301-307 (2010).
- 5. Perez C, et al. Translational control of cytoplasmic poly A binding protein (PABP) abundance in HCMV-infected cells, J Virol. Oct. 27, 2010 Epub.
- 6. Persson J, et al. Interleukin-1beta and tumour necrosis factor-alpha impede neutral lipid turnover in macrophage-derived foam cells, BMC Immunology, 9(7) (2008).
- 7. Vergne I, et al. Cell Biology of Mycobacterium tubercolosis Phagosome, Ann Rev Cell Dev Biol., Vol. 20, 367-94 (2004).
- 8. Moskowitz S M, et al. The Role of Pseudomonas Lipopolysaccharide in Cystic Fibrosis Airway Infection, Subcell Biochem., Vol. 53, 241-53 (2010).
- 9. Hall-Stoodley L, et al., Direct Detection of Bacterial Biofilms on the Middle-Ear Mucosa of Children With Chronic Otitis Media, JAMA, Vol. 256, No. 2, 202-11 (2006).
- 10. Franke-Fayard B, et al., Sequestration and Tissue Accumulation of Human Malaria Parasites: Can We Learn Anything from Rodent Models of Malaria?, PLoS Pathogens, Vol. 6, No. 9, e1001032 (2010).
- 11. Zhang S, et al. Delineation of Diverse Macrophage Activation Programs in Response to Intracellular Parasites and Cytokines, PLoS Negl Trop Dis, Vol. 4, No. 3: e648 (2010).
- 12. Ma Y, et al. NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly, J Virol. 82 (15) 7624-39 (2008).
- 13. Korant B D, Butterworth B E, Inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides, J Virol. 18(1):298-306 (1976).
- 14. U.S. Pat. No. 6,821,274 (2004).
- 15. International Publication No. WO2009/143411 (2009).
- 16. U.S. Pat. No. 5,601,526 (1997).
- 17. U.S. Pat. No. 6,067,859 (2000).
- 18. U.S. Pat. No. 7,751,057 (2010).
Claims (21)
1. A method of treating a condition associate with accumulation of an agent in cells in a patient, comprising exposing the cells comprising the accumulated agent to ultrasound, to selectively kill or induce apoptosis in the cells.
2. The method of claim 1 , wherein the cells are not AGE-modified cells.
3. The method of claim 1 , wherein the agent is selected from the group consisting of proteins, lipids, bacteria, viruses and parasites.
4. The method of claim 1 , wherein the cells are not tumor cells.
5. The method of claim 1 , wherein the cells are not cancerous.
6. The method of claim 1 , wherein the agent is selected from the group consisting of bacteria, viruses and parasites.
7. The method of claim 1 , wherein the agent is selected from the group consisting of proteins and lipids.
8. The method of claim 1 , wherein the cells are infected with a disease-causing organism.
9. The method of claim 8 , wherein the disease-causing organism is selected from the group consisting of bacteria, viruses and parasites.
10. The method of claim 1 , wherein the cells are blood cells.
11. The method of claim 10 , wherein the cells red blood cells.
12. The method of claim 10 , wherein the cells are white blood cells.
13. The method of claim 1 , further comprising testing the cells, to determine ultrasound frequency and power to selectively kill or induce apoptosis in the cells.
14. The method of claim 13 , wherein the testing comprises testing cells taken from the patient.
15. The method of claim 1 , wherein exposing the cells comprises exposing the cells to a plurality of ultrasound treatments.
16. The method of claim 1 , wherein the patient is infected with a disease-causing organism.
17. The method of claim 16 , wherein the disease-causing organism is selected from the group consisting of bacteria, viruses and parasites.
18. The method of claim 16 , wherein the agent is selected from the group consisting of proteins and lipids.
19. The method of claim 1 , wherein the condition is a chronic disease.
20. A method of removing cells from a sample, comprising:
exposing the sample to ultrasound, to selectively kill or induce apoptosis in the cells,
wherein the cells comprise an accumulated agent.
21. The method of claim 20 , wherein the sample is obtained from a patient.
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090076390A1 (en) * | 2005-11-23 | 2009-03-19 | Warren Lee | Integrated ultrasound imaging and ablation probe |
US8721571B2 (en) * | 2010-11-22 | 2014-05-13 | Siwa Corporation | Selective removal of cells having accumulated agents |
Family Cites Families (131)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4217344A (en) | 1976-06-23 | 1980-08-12 | L'oreal | Compositions containing aqueous dispersions of lipid spheres |
US4900747A (en) | 1984-03-19 | 1990-02-13 | The Rockefeller University | Method and agents for removing advanced glycosylation endproducts |
US5811075A (en) | 1984-03-19 | 1998-09-22 | The Rockefeller University | Method and agents for removing advanced glycosylation endproducts |
JP2644767B2 (en) | 1986-09-12 | 1997-08-25 | ザ ロックフェラー ユニバーシティ | Methods and agents for removing advanced glycosylation end products |
US4917951A (en) | 1987-07-28 | 1990-04-17 | Micro-Pak, Inc. | Lipid vesicles formed of surfactants and steroids |
US4911928A (en) | 1987-03-13 | 1990-03-27 | Micro-Pak, Inc. | Paucilamellar lipid vesicles |
US4965288A (en) | 1988-02-25 | 1990-10-23 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
IN172208B (en) | 1990-04-02 | 1993-05-01 | Sint Sa | |
US20040208826A1 (en) | 1990-04-02 | 2004-10-21 | Bracco International B.V. | Ultrasound contrast agents and methods of making and using them |
US20080063603A1 (en) | 1990-04-02 | 2008-03-13 | Bracco International B.V. | Ultrasound contrast agents and methods of making and using them |
US6372249B1 (en) | 1991-12-16 | 2002-04-16 | Baylor College Of Medicine | Senscent cell-derived inhibitors of DNA synthesis |
DE69214672T2 (en) | 1991-12-20 | 1997-04-03 | Technomed Medical Systems | SOUNDWAVE EMITTING, THERMAL EFFECTS AND CAVITATION EFFECTS DEVICE FOR ULTRASONIC THERAPY |
US5624804A (en) | 1991-12-20 | 1997-04-29 | The Rockefeller University | Immunochemical detection of In vivo advanced glycosylation end products |
WO1994000592A1 (en) | 1992-06-26 | 1994-01-06 | Exocell, Inc. | Monoclonal antibodies against glycated low density lipoprotein |
US5620479A (en) | 1992-11-13 | 1997-04-15 | The Regents Of The University Of California | Method and apparatus for thermal therapy of tumors |
US5518720A (en) | 1992-12-30 | 1996-05-21 | Exocell, Inc. | Treatment of complications of diabetes with substances reactive with the fructosyl-lysine structure in glycated albumin |
US6387373B1 (en) | 1993-01-15 | 2002-05-14 | Novavax, Inc. | Vaccines containing paucilsmellar lipid vesicles as immunological adjuvants |
EP0753071A1 (en) | 1993-04-28 | 1997-01-15 | Worcester Foundation For Experimental Biology | Cell-targeted lytic pore-forming agents |
US6410598B1 (en) | 1994-02-03 | 2002-06-25 | Michael P. Vitek | Compositions and methods for advanced glycosylation endproduct-mediated modulation of amyloidosis |
AU692237B2 (en) | 1994-02-03 | 1998-06-04 | Picower Institute For Medical Research, The | Compositions and methods for advanced glycosylation endproduct-mediated modulation of amyloidosis |
US5744318A (en) | 1994-12-30 | 1998-04-28 | Alteon Inc. | Monoclonal antibody for the detection of advanced glycosylation endproducts in biological samples |
DE69531311T2 (en) | 1994-12-30 | 2004-04-22 | Alteon Inc. | MONOCLONAL ANTIBODIES SPECIFIC FOR END PRODUCTS OF ADVANCED GLYCOSYLATION IN BIOLOGICAL SAMPLES |
US6176842B1 (en) * | 1995-03-08 | 2001-01-23 | Ekos Corporation | Ultrasound assembly for use with light activated drugs |
AU6907496A (en) | 1995-08-25 | 1997-03-19 | Case Western Reserve University | Process for detecting pentosidine and for assessing the biological age of a biological sample |
JP3579549B2 (en) | 1995-10-24 | 2004-10-20 | 株式会社トクヤマ | Use as a marker for diabetes or diabetic complications |
US6090382A (en) | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
US5664570A (en) | 1996-02-20 | 1997-09-09 | Svc | Apparatus for applying high-intensity ultrasonic waves to a target volume within a human or animal body |
US5908925A (en) | 1996-06-27 | 1999-06-01 | Exocell, Inc. | Genetically engineered immunoglobulins with specificity for glycated albumin |
US5984882A (en) | 1996-08-19 | 1999-11-16 | Angiosonics Inc. | Methods for prevention and treatment of cancer and other proliferative diseases with ultrasonic energy |
US6261537B1 (en) | 1996-10-28 | 2001-07-17 | Nycomed Imaging As | Diagnostic/therapeutic agents having microbubbles coupled to one or more vectors |
US7258857B2 (en) | 1996-11-22 | 2007-08-21 | The Trustees Of Columbia University In The City Of New York | Rage-related methods for treating inflammation |
US6245318B1 (en) | 1997-05-27 | 2001-06-12 | Mallinckrodt Inc. | Selectively binding ultrasound contrast agents |
US7101838B2 (en) | 1997-08-05 | 2006-09-05 | The Trustees Of Columbia University In The City Of New York | Method to prevent accelerated atherosclerosis using (sRAGE) soluble receptor for advanced glycation endproducts |
CN1270637A (en) | 1997-08-08 | 2000-10-18 | 华盛顿大学 | Isolation of a novel senescence-factor gene, P23 |
US6380165B1 (en) | 1997-09-19 | 2002-04-30 | The Picower Institute For Medical Research | Immunological advanced glycation endproduct crosslink |
US6896659B2 (en) | 1998-02-06 | 2005-05-24 | Point Biomedical Corporation | Method for ultrasound triggered drug delivery using hollow microbubbles with controlled fragility |
JP4016304B2 (en) | 1998-02-26 | 2007-12-05 | 日本油脂株式会社 | Monoclonal antibody, hybrid cell, and method for producing monoclonal antibody |
WO1999064463A1 (en) | 1998-06-09 | 1999-12-16 | Alteon Inc. | Monoclonal antibodies specific for guanidino group-derived advanced glycosylation endproducts in biological samples |
US6753150B2 (en) | 1998-10-05 | 2004-06-22 | The Trustees Of Columbia University In The City Of New York | Method for determining whether a compound is capable of inhibiting the interaction of a peptide with rage |
EP1121454B1 (en) | 1998-10-06 | 2007-11-14 | The Trustees of Columbia University in the City of New York | Extracellular novel rage binding protein (en-rage) and uses thereof |
US6309355B1 (en) * | 1998-12-22 | 2001-10-30 | The Regents Of The University Of Michigan | Method and assembly for performing ultrasound surgery using cavitation |
US6067859A (en) | 1999-03-04 | 2000-05-30 | The Board Of Regents, The University Of Texas System | Optical stretcher |
BR122014028365B8 (en) | 1999-06-25 | 2021-07-06 | Genentech Inc | manufactured article comprising a first container comprising a composition of humab4d5-8 contained therein and a second container comprising a composition of rhumab 2c4 contained therein |
CA2382095A1 (en) | 1999-08-13 | 2001-02-22 | The Trustees Of Columbia University In The City Of New York | Methods of inhibiting binding of .beta.-sheet fibril to rage and consequences thereof |
WO2001018060A1 (en) | 1999-09-08 | 2001-03-15 | Toray Industries, Inc. | Materials for extracorporeal circulation, adsorbents for diabetic complication factors, containers for eliminating diabetic complication factors and method of eliminating diabetic complication factors |
US6853864B2 (en) | 2000-02-02 | 2005-02-08 | Catholic University Of America, The | Use of electromagnetic fields in cancer and other therapies |
EP1283728A2 (en) | 2000-05-23 | 2003-02-19 | Amersham Health AS | Contrast agents |
NO312338B1 (en) | 2000-08-25 | 2002-04-29 | Gunnar Myhr | Device for selective cell or virus destruction in a living organism |
CN2445326Y (en) | 2000-10-09 | 2001-08-29 | 刘永详 | Immune analysis device for assaying saccharified protein |
US6676963B1 (en) | 2000-10-27 | 2004-01-13 | Barnes-Jewish Hospital | Ligand-targeted emulsions carrying bioactive agents |
US6821274B2 (en) | 2001-03-07 | 2004-11-23 | Gendel Ltd. | Ultrasound therapy for selective cell ablation |
US7481781B2 (en) | 2000-11-17 | 2009-01-27 | Gendel Limited | Ultrasound therapy |
WO2002054018A2 (en) * | 2001-01-03 | 2002-07-11 | Ultrashape Inc. | Non-invasive ultrasonic body contouring |
US7347855B2 (en) * | 2001-10-29 | 2008-03-25 | Ultrashape Ltd. | Non-invasive ultrasonic body contouring |
DE60202008T2 (en) | 2001-03-22 | 2005-12-01 | Roche Diagnostics Gmbh | A method of finding reagents and solid phase components in specific binding assays free of advanced glycosylation endproducts |
US20040210042A1 (en) | 2001-07-19 | 2004-10-21 | Tsuchida Jun-Ichi | Polypeptides relating to signal transfer of advanced glycation end product receptor |
JP4012722B2 (en) | 2001-11-22 | 2007-11-21 | 株式会社トランスジェニック | Antibodies against carboxymethylated peptides |
MY139983A (en) | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
AU2003254650B2 (en) | 2002-07-24 | 2010-09-09 | Qlt, Inc. | Pyrazolylbenzothiazole derivatives and their use as therapeutic agents |
WO2004016229A2 (en) | 2002-08-16 | 2004-02-26 | Wyeth | Compositions and methods for treating rage-associated disorders |
US20070128117A1 (en) | 2003-02-04 | 2007-06-07 | Bracco International B.V. | Ultrasound contrast agents and process for the preparation thereof |
AU2004215125B2 (en) | 2003-02-26 | 2011-01-06 | Institute For Research In Biomedicine | Monoclonal antibody production by EBV transformation of B cells |
WO2004079368A2 (en) | 2003-03-08 | 2004-09-16 | Auvation Ltd | Markers for colorectal cancer |
WO2005009256A2 (en) | 2003-07-31 | 2005-02-03 | Woodwelding Ag | Method and device for promotion of tissue regeneration on wound surfaces |
US7358226B2 (en) | 2003-08-27 | 2008-04-15 | The Regents Of The University Of California | Ultrasonic concentration of drug delivery capsules |
WO2005070472A2 (en) | 2004-01-20 | 2005-08-04 | Sunnybrook And Women's College Health Sciences Centre, | High frequency ultrasound imaging using contrast agents |
WO2005079463A2 (en) | 2004-02-17 | 2005-09-01 | Dynamis Therapeutics, Inc. | Fructoseamine 3 kinase and the formation of collagen and elastin |
WO2006012415A2 (en) | 2004-07-20 | 2006-02-02 | Critical Therapeutics, Inc. | Rage protein derivatives |
WO2006017647A1 (en) | 2004-08-03 | 2006-02-16 | Transtech Pharma, Inc. | Rage fusion proteins and methods of use |
GB0422525D0 (en) | 2004-10-11 | 2004-11-10 | Luebcke Peter | Dermatological compositions and methods |
GT200600031A (en) | 2005-01-28 | 2006-08-29 | ANTI-BETA ANTIBODY FORMULATION | |
WO2006094951A1 (en) | 2005-03-03 | 2006-09-14 | Bracco Research Sa | Medical imaging system based on a targeted contrast agent |
JP2006249016A (en) | 2005-03-11 | 2006-09-21 | Fujio Goto | Plant infectious disease controlling agent and fungal external preparation each derived from organic residue |
KR20070094950A (en) | 2005-04-05 | 2007-09-27 | 가부시끼가이샤 제이엠에스 | Antibody reactive specifically to age derived from 3,4-dge |
US20070225242A1 (en) | 2005-06-21 | 2007-09-27 | The Board Of Trustees Of The Leland Stanford Junior University | Method and composition for treating and preventing tumor metastasis in vivo |
US20070059247A1 (en) | 2005-08-30 | 2007-03-15 | Lindner Jonathan R | Deposit contrast agents and related methods thereof |
US20070065415A1 (en) | 2005-09-16 | 2007-03-22 | Kleinsek Donald A | Compositions and methods for the augmentation and repair of defects in tissue |
US20070083120A1 (en) | 2005-09-22 | 2007-04-12 | Cain Charles A | Pulsed cavitational ultrasound therapy |
US20070078290A1 (en) | 2005-09-30 | 2007-04-05 | Esenaliev Rinat O | Ultrasound-based treatment methods for therapeutic treatment of skin and subcutaneous tissues |
JP4779115B2 (en) | 2005-12-16 | 2011-09-28 | 国立大学法人東北大学 | Postoperative prognostic method for early lung cancer |
EP1988918A4 (en) | 2006-02-22 | 2010-04-28 | Novavax Inc | Adjuvant and vaccine compositions |
US9056905B2 (en) | 2007-05-21 | 2015-06-16 | Alderbio Holdings Llc | Antibodies to TNF-α and use thereof |
WO2008154638A2 (en) | 2007-06-12 | 2008-12-18 | Board Of Regents, The University Of Texas System | Antagonists of the receptor for advanced glycation end-products (rage) |
PL2158210T3 (en) | 2007-06-14 | 2016-08-31 | Galactica Pharmaceuticals Inc | Rage fusion proteins |
US20120156134A1 (en) | 2007-12-20 | 2012-06-21 | Shayne Squires | Compositions and methods for detecting or eliminating senescent cells to diagnose or treat disease |
US7751057B2 (en) | 2008-01-18 | 2010-07-06 | The Board Of Trustees Of The University Of Illinois | Magnetomotive optical coherence tomography |
US8235418B2 (en) | 2008-02-12 | 2012-08-07 | Tk Holdings Inc. | Airbag |
DE102008009461A1 (en) | 2008-02-15 | 2009-08-20 | Beiersdorf Ag | Reducing the wrinkle, comprises applying a cosmetic preparation on the skin to be treated and subsequently working up by means of an ultrasonic applicator |
KR101649189B1 (en) | 2008-05-09 | 2016-08-18 | 애브비 인코포레이티드 | Antibodies to receptor of advanced glycation end products (RAGE) and uses thereof |
AU2014202548A1 (en) | 2008-05-23 | 2014-05-29 | Siwa Corporation | Methods, compositions and apparatuses for facilitating regeneration |
ES2499395T3 (en) | 2008-05-23 | 2014-09-29 | Siwa Corporation | Procedures to facilitate regeneration |
JP5229473B2 (en) * | 2008-06-04 | 2013-07-03 | 財団法人ヒューマンサイエンス振興財団 | Ultrasound medical equipment |
US20110319499A1 (en) | 2008-06-30 | 2011-12-29 | The Johns Hopkins University | Methods for the Detection of Advanced Glycation Endproducts and Markers for Disease |
US8343420B2 (en) * | 2009-09-17 | 2013-01-01 | Sanuwave, Inc. | Methods and devices for cleaning and sterilization with shock waves |
EP2493486A1 (en) | 2009-10-30 | 2012-09-05 | University Of Arkansas For Medical Science | Use of autologous effector cells and antibodies for treatment of multiple myeloma |
CA2795740C (en) | 2010-04-14 | 2018-03-13 | Microvention, Inc. | Implant delivery device |
US9662347B2 (en) | 2010-05-11 | 2017-05-30 | Gachon University Of Industry-Academic Cooperation Foundation | Method for inhibiting the induction of cell death by inhibiting the synthesis or secretion of age-albumin in cells of the mononuclear phagocyte system |
EP3511017A1 (en) | 2010-09-27 | 2019-07-17 | Siwa Corporation | Selective removal of age-modified cells for treatment of atherosclerosis |
WO2012135616A1 (en) | 2011-03-31 | 2012-10-04 | Siwa Corporation | Vaccination against advanced glycation end-products |
UA112434C2 (en) | 2011-05-27 | 2016-09-12 | Ґлаксо Ґруп Лімітед | ANTIGENCY BINDING SPECIFICALLY Binds to ALL |
US8858471B2 (en) | 2011-07-10 | 2014-10-14 | Guided Therapy Systems, Llc | Methods and systems for ultrasound treatment |
US8954155B2 (en) | 2011-09-19 | 2015-02-10 | Biotalk Technologies Inc | Apparatus and method for rejuvenating skin |
CN103857697A (en) | 2011-09-23 | 2014-06-11 | 伍兹堡尤利乌斯-马克西米利安斯大学 | Peptide or arrangement of peptides forming a staphylococcus aureus epitope binding site |
US20140322216A1 (en) | 2011-11-08 | 2014-10-30 | The Trustees Of The University Of Pennsylvania | Glypican-3-specific antibody and uses thereof |
KR101939401B1 (en) | 2011-11-10 | 2019-01-16 | 가천대학교 산학협력단 | Composition for preventing or treating ischemic cardiac diseases comprising inhibiting agent for synthesis or secretion of AGE-albumin of mononuclear phagocyte as active ingredient |
US20130288980A1 (en) | 2012-04-02 | 2013-10-31 | Buck Institute For Research On Aging | Targeting senescent and cancer cells for selective killing by interference with foxo4 |
CA2902298A1 (en) | 2013-03-06 | 2014-09-12 | Protalix Ltd. | Chimeric polypeptides, polynucleotides encoding same, cells expressing same and methods of producing same |
JP2015076575A (en) | 2013-10-11 | 2015-04-20 | 株式会社日本自動車部品総合研究所 | Cooler |
WO2015108998A2 (en) | 2014-01-15 | 2015-07-23 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Cartilage targeting agents and their use |
EP3096824A1 (en) | 2014-01-24 | 2016-11-30 | Cole Research&Design, Inc. | Oral suction device |
CA2939121C (en) | 2014-01-28 | 2020-11-24 | Mayo Foundation For Medical Education And Research | Effective treatment of osteoarthritis, pulmonary disease, ophthalmic disease, and atherosclerosis by removing senescent cells at the site of the disease |
DE102014107077B3 (en) | 2014-05-20 | 2015-08-13 | Ecs Engineered Control Systems Ag | switching device |
US10238742B2 (en) | 2014-06-25 | 2019-03-26 | Yale University | Cell penetrating nucleolytic antibody based cancer therapy |
ES2908203T3 (en) | 2014-09-19 | 2022-04-28 | Siwa Corp | Anti-aging antibodies for the treatment of inflammation and autoimmune disorders |
WO2016061532A1 (en) | 2014-10-16 | 2016-04-21 | The Broad Institute Inc. | Compositions and methods for identifying and treating cachexia or pre-cachexia |
US9993535B2 (en) | 2014-12-18 | 2018-06-12 | Siwa Corporation | Method and composition for treating sarcopenia |
US10358502B2 (en) | 2014-12-18 | 2019-07-23 | Siwa Corporation | Product and method for treating sarcopenia |
US10889634B2 (en) | 2015-10-13 | 2021-01-12 | Siwa Corporation | Anti-age antibodies and methods of use thereof |
CA3000815C (en) | 2015-10-13 | 2022-11-01 | Siwa Corporation | Anti-age antibodies and methods of use thereof |
CN105430512A (en) | 2015-11-06 | 2016-03-23 | 腾讯科技(北京)有限公司 | Method and device for displaying information on video image |
KR102503910B1 (en) | 2015-11-09 | 2023-02-27 | 삼성전자주식회사 | Method and apparatus of standing assistance |
KR20230074837A (en) | 2016-02-19 | 2023-05-31 | 시와 코퍼레이션 | Method and composition for treating cancer, killing metastatic cancer cells and preventing cancer metastasis using antibody to advanced glycation end products(age) |
KR20180133452A (en) | 2016-04-15 | 2018-12-14 | 시와 코퍼레이션 | Anti-aging antibodies to treat neurodegenerative diseases |
US11213585B2 (en) | 2016-06-23 | 2022-01-04 | Siwa Corporation | Vaccines for use in treating various diseases and disorders |
US10858449B1 (en) | 2017-01-06 | 2020-12-08 | Siwa Corporation | Methods and compositions for treating osteoarthritis |
JP2020516648A (en) | 2017-04-13 | 2020-06-11 | シワ コーポレーション | Humanized monoclonal advanced glycation end product antibody |
JP2020521117A (en) | 2017-05-04 | 2020-07-16 | シワ コーポレーション | Antibody for advanced glycation end products |
US20220175916A1 (en) | 2018-07-23 | 2022-06-09 | Siwa Corporation | Methods and compositions for treating chronic effects of radiation and chemical exposure |
US20210253739A1 (en) | 2018-08-23 | 2021-08-19 | Siwa Corporation | Anticarboxymethyl lysine antibodies and ultrasound for removing age-modified cells |
JP7372644B2 (en) | 2018-12-27 | 2023-11-01 | アクア株式会社 | refrigerator |
-
2010
- 2010-11-22 US US12/951,768 patent/US8721571B2/en active Active
-
2011
- 2011-11-18 AU AU2011332143A patent/AU2011332143B2/en active Active
- 2011-11-18 CA CA2818647A patent/CA2818647C/en active Active
- 2011-11-18 WO PCT/US2011/061387 patent/WO2012071269A2/en active Application Filing
-
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- 2013-06-18 ZA ZA2013/04478A patent/ZA201304478B/en unknown
-
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- 2014-04-07 US US14/247,081 patent/US9320919B2/en active Active
-
2015
- 2015-10-22 US US14/920,737 patent/US10960234B2/en active Active
-
2021
- 2021-02-16 US US17/177,140 patent/US20210236860A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090076390A1 (en) * | 2005-11-23 | 2009-03-19 | Warren Lee | Integrated ultrasound imaging and ablation probe |
US8721571B2 (en) * | 2010-11-22 | 2014-05-13 | Siwa Corporation | Selective removal of cells having accumulated agents |
US9320919B2 (en) * | 2010-11-22 | 2016-04-26 | Siwa Corporation | Selective removal of cells having accumulated agents |
US10960234B2 (en) * | 2010-11-22 | 2021-03-30 | Siwa Corporation | Selective removal of cells having accumulated agents |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11261241B2 (en) | 2008-05-23 | 2022-03-01 | Siwa Corporation | Methods, compositions and apparatuses for facilitating regeneration |
US11872269B2 (en) | 2014-12-18 | 2024-01-16 | Siwa Corporation | Method and composition for treating sarcopenia |
US11873345B2 (en) | 2014-12-18 | 2024-01-16 | Siwa Corporation | Product and method for treating sarcopenia |
US11833202B2 (en) | 2016-02-19 | 2023-12-05 | Siwa Corporation | Method and composition for treating cancer, killing metastatic cancer cells and preventing cancer metastasis using antibody to advanced glycation end products (AGE) |
US11958900B2 (en) | 2016-04-15 | 2024-04-16 | Siwa Corporation | Anti-age antibodies for treating neurodegenerative disorders |
US11213585B2 (en) | 2016-06-23 | 2022-01-04 | Siwa Corporation | Vaccines for use in treating various diseases and disorders |
US11542324B2 (en) | 2017-04-13 | 2023-01-03 | Siwa Corporation | Humanized monoclonal advanced glycation end-product antibody |
US11518801B1 (en) | 2017-12-22 | 2022-12-06 | Siwa Corporation | Methods and compositions for treating diabetes and diabetic complications |
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US9320919B2 (en) | 2016-04-26 |
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WO2012071269A2 (en) | 2012-05-31 |
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US20140303526A1 (en) | 2014-10-09 |
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