WO2001082871A2 - Methode d'utilisation d'isotope de zinc dans la therapie et le diagnostique du cancer du colon - Google Patents

Methode d'utilisation d'isotope de zinc dans la therapie et le diagnostique du cancer du colon Download PDF

Info

Publication number
WO2001082871A2
WO2001082871A2 PCT/US2001/014664 US0114664W WO0182871A2 WO 2001082871 A2 WO2001082871 A2 WO 2001082871A2 US 0114664 W US0114664 W US 0114664W WO 0182871 A2 WO0182871 A2 WO 0182871A2
Authority
WO
WIPO (PCT)
Prior art keywords
zinc
colon cancer
isotope
cells
cancer cells
Prior art date
Application number
PCT/US2001/014664
Other languages
English (en)
Other versions
WO2001082871A3 (fr
Inventor
David Tsai
Original Assignee
Ambryx Biotechnology, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ambryx Biotechnology, Inc. filed Critical Ambryx Biotechnology, Inc.
Publication of WO2001082871A2 publication Critical patent/WO2001082871A2/fr
Publication of WO2001082871A3 publication Critical patent/WO2001082871A3/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
    • A61K51/0476—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group complexes from monodendate ligands, e.g. sestamibi

Definitions

  • This invention relates generally to treatment and diagnosis of cancer, and more specifically to treatment and diagnosis of colon cancer.
  • Zinc is an important nutrient and is necessary to maintain a multitude of physiologic processes in the body. Mineral supplements are often used by people to ensure that the body has a sufficient level of zinc. Zinc is used in the treatment of two diseases . The only two diseases known to be treated with zinc are Wilson's disease and acrodermatitis enteropathica. The use of zinc therapy for these diseases has demonstrated the exceptional safety and efficacy of zinc when used for a long period of time, namely, forty (40) years. (Anderson, et al . The Annals of Pharmacotherapy, Vol 32, pp. 78-87, January 1998).
  • the cancer Before cancer can be treated in a patient, the cancer must first be diagnosed. Early cancer diagnosis is sometimes a critical factor in the treatment of the cancer. If the cancer is detected in its early stages, then there is a greater chance of successful treatment. Thus, the need for new cancer diagnostic techniques is as equally important as the need for new cancer treatment .
  • the present invention introduces such refinement by inducing apoptosis in colon cancer cells by exposing them to zinc.
  • Apoptosis is an active process of gene-directed cellular self- destruction, also called programmed cell death.
  • Programmed cell death is different than cell death caused by cell injury, which is called necrosis. Necrosis is not desirable because cell death through necrosis causes inflammation in the surrounding tissue.
  • Apoptosis plays an important role in the human body from the early stages of embryonic development to the inevitable decline associated with old age. In normal adult tissue, apoptosis occurs continuously in slowly proliferating cell populations such as hepatic and adrenal cortical epithelium as well as in rapidly proliferating populations such as intestinal crypt epithelium and differentiating spermatogoni .
  • the present invention in a first of its preferred embodiments includes a method of inducing apoptosis in colon cancer cells by administering zinc to the colon cancer cells .
  • the source of the zinc be one or a combination of the following: zinc acetate, zinc chloride, and/or zinc sulfate.
  • the invention includes a method of inducing apoptosis in colon cancer cells by administering zinc and a phosphate binder to the colon cancer cells.
  • the inclusion of the phosphate binder increases the apoptosis-inducing activity of zinc. It was observed that when zinc acetate was dissolved in phosphate buffer solution, a white precipitate was formed. This suggests that the zinc acetate is instable in phosphate solution. The precipitate that is formed is zinc phosphate, a water-insoluble chemical. Based on this observation, it was reasoned that phosphate interferes with zinc. To test this reasoning, calcium acetate (a phosphate binder) was added to the zinc acetate solution and then administered to the colon cancer cells—the apoptosis-inducing activity of zinc acetate in colon cancer cells increased three to four times.
  • the phosphate binder be either calcium acetate and/or calcium carbonate, alone or in combination. Although these are the preferred phosphate binders, any chemical that removes phosphate from the solution and does not interfere with the activity of zinc is acceptable. It is also preferred that the source of the zinc be zinc acetate, zinc chloride, and zinc sulfate, alone or in combination.
  • the invention includes a method of treating colon cancer by administering isotopic zinc to the colon cancer cells .
  • Isotopic zinc emits radiation energy which can be captured by radiation measuring techniques such as a gamma camera.
  • the zinc isotopes have a relatively short half-life such as the zinc isotope, zinc-62.
  • the radiation level be about 1000-3000 cGy.
  • Non-isotopic zinc and isotopic zinc can be combined to treat colon cancer.
  • a phosphate binder can be combined with the treatment using only isotopic zinc or with the combination of isotopic and non-isotopic zinc. The addition of the phosphate binder enhances the apoptotic activity of both the isotopic and non-isotopic zinc.
  • the invention includes a method of diagnosing colon cancer by administering isotopic zinc to the colon cancer cells and using radionuclide imaging techniques to measure the isotopic zinc accumulated in the colon cancer cells.
  • Radionuclide imaging depends on the fact that certain substances selectively accumulate in different parts of the body. (Armstrong, et al. Diagnostic Imaging, 2d ed. , pp. 6- 7) .
  • Zinc selectively accumulates in colon cancer cells and not in normal colon cells.
  • radionuclide imaging techniques can be used to detect isotopic zinc accumulated in colon cancer cells.
  • the zinc isotopes have a relatively short half-life to minimize the patient's exposure to the radiation emitted by the zinc isotopes. It is preferred that the source of the zinc isotopes be zinc-62, having a half-life of 9.26 hours. Furthermore, the practitioner will select a radiation level that will allow the selected imaging technique to effectively image the colon cancer and that will minimize the patient's exposure to radiation.
  • Fig. 1 is a photograph taken through a phase-contrast microscope of colon cancer cells (HT-29) in growth medium and control buffer- (saline solution) ;
  • Fig. 2 is a photograph taken through a phase-contrast microscope of colon cancer cells (HT-29) after zinc acetate (in saline) has been administered and the HT-29 cells have undergone apoptosis;
  • Fig. 3 is a photograph taken through a fluorescence microscope of colon cancer cells (HT-29) stained with Hoechst dye in saline solution;
  • Fig. 4 is a photograph taken through a fluorescence microscope of colon cancer cells (HT-29) after zinc acetate (in saline) has been administered and the colon cancer cells have undergone apoptosis, the cells have been stained with Hoechst dye;
  • Fig. 5 is a photograph taken through a phase-contrast microscope of colon cancer cells (T-84) in growth medium and control buffer (saline solution) ;
  • Fig. 6 is a photograph taken through a phase-contrast microscope of colon cancer cells (T-84) after having zinc acetate , _
  • Fig. 7 is a photograph taken through a phase-contrast microscope of normal colon cells (CCD 18 Co) in growth medium and control buffer (saline solution) ;
  • Fig. 8 is a photograph taken through a phase-contrast microscope of normal colon cells (CCD 18 Co) after zinc acetate (in saline) was administered to the cells;
  • HT-29 (ATCC cell line number HTB 38) , is a cell derived from a human colon tumor, and was used to test the biological activity of zinc. In order to test the activity of zinc, two plates of one thousand (1,000) HT-29 cells were seeded in 10 microliters of McCoy 5A medium containing ten percent (10%) fetal bovine serum, penicillin and streptomycin at 37 degrees Celsius in 5% C0 2
  • Fig. 1 shows that the one thousand HT-29 cells in saline solution are healthy and normal.
  • Fig. 2 clearly demonstrates -the death of the HT-29 colon cancer cells. To confirm that the HT-29 cell death induced by zinc was caused by apoptosis (programmed cell death) rather than necrosis (cell injury), another assay was done.
  • Fig. 4 confirms that the colon cancer cells have undergone apoptosis because the nuclei of the cells show the characteristics of apoptosis.
  • the zinc acetate caused the condensation of the nucleus, this is demonstrated by the more intense fluorescent light displayed by Fig. 4 as compared to Fig. 3.
  • the nuclear condensation is accompanied by the fragmentation of the DNA which is demonstrated by the breakage of the nucleus.
  • some of the nuclear fragments show peripheral crescents of compacted chromatin, a characteristic of a cell that has undergone apoptosis .
  • T-84 (ATCC cell line number CCL 248) is another type of colon cancer cell that was used to test the biological activity of zinc.
  • two plates of T-84 cells were seeded in 10 microliters of 1:1 mixture of Ham's F12 medium and DMEM medium containing ten percent (10%) fetal bovine serum, penicillin and streptomycin at 37 degrees Celsius in 5% CO microtray plates (25 ⁇ l wells, Robbins Scientific
  • Fig. 5 shows that the one thousand T- 84 cells in saline solution are healthy and normal.
  • Fig. 6 clearly demonstrates the death of the T-84 colon cancer cells.
  • CCD 18 Co ATCC cell line number CRL 1459
  • normal human colon cells in lO ⁇ l of 1:1 mixture of Ham's F12 medium and DMEM medium containing 10% fetal bovine serum, penicillin and streptomycin at 37 degree Celsius in 5% CO choir microtray plates (25 ⁇ l wells, Robbins Scientific Corp.) .
  • Cells in both plates were grown for 24 hours.
  • Saline solution (5 ⁇ l) was added to the first plate and incubated for eight (8) hours. After eight hours the cells were photographed (Fig. 7) under a phase-contrast microscope.
  • Fig. 7 shows that the CCD 18 Co cells are healthy and normal.
  • a photograph of the second plate (Fig. 8) was taken under a phase-contrast microscope. Fig. 8 shows that the normal colon cells have not been affected by the zinc, they are normal and healthy.
  • zinc acetate would induce apoptosis in, a variety of different cell lines were tested. As shown in the chart below, zinc acetate induced apoptosis selectively in human colon cancer cells .
  • Cell lines I .Choriocarcinoma (JEG-3). 2. Prostate cancer (LNCaP). 3.Hepatocarcinoma (Hep G2).
  • Colon adenocarcinoma (Colo 205).
  • CHART I % of apoptotic cells Number of cells with DNA. condensation and fragmentation
  • the zinc acetate did not induce apoptosis in normal cells such as the human lung fibroblast (CCD 39 Lu) , the human lung cells (Wi 38) or the normal colon fibroblast (CCD 18Co) .
  • Chart II demonstrates that zinc induces apoptosis in a dose- dependent manner and that addition of a phosphate binder increases the apoptosis-inducing activity of zinc. Two different assays were done, and the results are illustrated in Chart II. In the first assay the HT-29 cells were incubated with various concentrations of zinc acetate for six (6) hours. In the second assay the HT-29 cells were incubated with various concentrations of zinc acetate and calcium acetate for six (6) hours.
  • Chart III is a similar assay using T-84 colon cancer cells. Chart III shows the dose-dependence of inducing apoptosis in T-84 cells by zinc acetate. It also shows that adding a phosphate binder to the assay greatly increases the apoptosis-inducing activity of the zinc. In the absence of calcium acetate (a phosphate binder), the LD for the induction of apoptosis in the T-84 cells is a dose of zinc of 50uM. In the presence of calcium acetate the LD is 25 ⁇ M.
  • Chart IV demonstrates that zinc acetate rapidly induces apoptosis in colon cancer cells.
  • the concentration of the zinc acetate used in this assay was 68 ⁇ M.
  • the zinc acetate induced apoptosis in fifty percent (50%) of the colon cancer cells (HT-29) in six (6) hours.
  • the zinc acetate induced apoptosis in ninety-five percent (95%) of the colon cancer ce]_,ls in six (6) hours.
  • the concentration of zinc that appears to be useful in inducing apoptosis in colon cancer cells, in the absence of a phosphate binder is from about 60 ⁇ M to about 80 ⁇ M.
  • the concentration of zinc that appears to be useful in inducing apoptosis in colon cancer cells, in the presence of a phosphate binder is from about 20 ⁇ M to about 50 ⁇ M.
  • Zinc induces apoptosis in colon cancer cell lines in vitro.
  • the concentration of zinc for the induction of 50% cell death in colon cancer cells is estimated to be about 68 ⁇ M without a phosphate binder, and about 20 ⁇ M with a phosphate binder.
  • Published studies reveal that these concentrations can be easily reached in vivo by oral administration of zinc acetate.
  • plasma zinc concentration was found to reach 169 ⁇ M by oral administration of 200 mg of zinc per day in a dog. (Brewer et al., Use of Zinc Acetate to Treat Copper Toxicosis in Dogs, JAVMA 1992, pp. 564-567, Vol. 201 no. 4).
  • Phosphate interferes with the apoptosis-inducing activity of zinc. Hence, phosphate may diminish the effect of zinc on colon cancer cells.
  • the phosphate concentration was about 3 to 5 mM, whereas the serum phosphate concentration is 2mM.
  • normal colon cells CCD 18 Co
  • both plates the normal colon cells were grown in Eagle's MEM with non-essential amino acids and Earle's BSS containing 10% fetal bovine serum.
  • the cells were incubated with zinc acetate at a final concentration of 25 ⁇ M for 15 hours.
  • the cells of both plates were washed with PBS three times.
  • the cells were then grown in the same growth media and stained with BTC-5 dye at a final concentration of 1 ⁇ M.
  • BTC-5 is a cell-permeant dye that emits fluorescent light when it is exposed to heavy metals such as zinc and mercury. BTC-5 dye can be used to determine intracellular zinc.
  • the first tray containing the normal colon cells not incubated with zinc and stained with BTC-5 was photographed under a fluorescent microscope.
  • the second tray containing the normal colon cells incubated with zinc and stained with BTC-5 was photographed under a fluorescent microscope. Comparing the photograph of the second tray to the photograph of the first tray shows no significant increase in fluorescent light. Thus, it can be concluded that no significant amount of zinc was taken up by the normal colon cells (CCD 18 Co) after 15 hours of incubation with 25 uM zinc acetate.
  • colon cancer cells colon cancer cells (HT-29) were grown in McCoy's 5a medium containing 10% fetal bovine serum in a 96 wells plate. In one of two plates containing colon cancer cells, the colon cancer cells were incubated with zinc acetate at a final concentration of 25 uM for 15 hours. After the incubation, the colon cancer cells were washed with PBS three times. The cells were then grown in the same medium and stained with the BTC-5 dye.
  • the first tray containing the colon cancer cells not incubated with zinc and stained with BTC-5 was photographed under a fluorescent'"microscope.
  • the second tray containing the colon cancer cells incubated with zinc acetate and stained with BTC-5 was photographed under a fluorescent microscope .
  • the photograph of the second tray, as compared to the photograph of the first tray, shows a significant increase in fluorescent light. It can be concluded that a significant amount of zinc was taken up by the colon cancer cells after 15 hours of incubation with 25 ⁇ M of zinc acetate. The results suggest that zinc selectively accumulates in colon cancer cells, and not normal colon cells.
  • Radionuclide imaging technique is a medical diagnostic imaging tool that works with radioactive isotopes. Radioactive isotopes emit gamma rays that can be detected by a gamma camera. When the gamma rays strike the gamma camera, an image is eventually produced. Imaging techniques that use gamma rays to image can be used to image colon cancer cells .
  • the isotopic zinc When isotopic zinc is injected into the body, the isotopic zinc selectively accumulates within colon cancer cells.
  • the isotopic zinc accumulated within colon cancer cells emit gamma rays.
  • the gamma rays can then be captured by a gamma camera, or other gamma ray capturing devices .
  • the resultant images from the gamma camera can be used to diagnose the colon dancer cells.
  • isotopic zinc may also be used in treating colon cancer.
  • Isotopic zinc emits radioactive energy. Administered to cells, the radiation from isotopic zinc kills the cells.
  • the isotopic zinc When isotopic zinc is injected into the body, the isotopic zinc selectively accumulates in colon cancer cells. Once accumulated in the colon cancer cells, the radiation from the isotopic zinc kills the colon cancer cells.
  • the radiation level that appears to be safe is from about 1000-3000 cGy, depending on the size and stage of the tumor. Although a ' radiation level above 3000 cGy may be used, such level may have deleterious effects on healthy human cells.
  • the radiation level that a practitioner selects will vary depending upon the imaging technique used. As the practitioner strives to minimize the patient's exposure to radiation, the practitioner will select a radiation level that will yield effective imaging of the colon cancer. As cancer imaging techniques advance and improve, lower radiation levels will be needed for effective imaging.
  • the isotopic zinc have a half-life of a few hours or a few days, such as the zinc isotope zinc-62.
  • Zinc-62 has a-half-life of 9.26 hours.
  • Zinc-62 emits gamma radiation that can be detected by a gamma camera and thus imaged.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une méthode d'induction de l'apoptose dans les cellules cancéreuse du colon par administration de zinc auxdites cellules. Le zinc peut être sous la forme d'un acétate de zinc, chlorure de zinc et sulfate de zinc, ou une combinaison de ceux-ci. La concentration de zinc peut se situer entre environ 60νM et environ 80νM. L'apoptose induisant l'activité du zinc sur les cellules cancéreuses du colon est augmentée deux à trois fois en administrant aussi un chélateur de phosphore avec le zinc aux cellules cancéreuses du colon. Le chélateur de phosphore peut être un acétate de calcium et un carbonate de calcium, ou une combinaison de ceux-ci. Si le zinc et un chélateur de phosphore sont administrés aux cellules cancéreuses du colon, la concentration de zinc se situe alors entre environ 20νM et environ 50νM. Une méthode de traitement du cancer du colon par administration de zinc isotopique aux cellules cancéreuses du colon, ou en combinaison avec du zinc non isotopique. Le zinc isotopique est choisi dans le groupe constitué d'isotopes de zinc possédant une courte demi-vie, tels que du zinc 62. Le chélateur de phosphore peut être combiné de manière à augmenter l'activité du zinc isotopique. Cette invention concerne enfin une méthode de diagnostique des cellules cancéreuses du colon par administration de zinc isotopique aux cellules cancéreuses du colon et par utilisation de la technique d'imagerie isotopique afin de mesurer le zinc isotopique accumulé dans les cellules cancéreuses du colon. Afin de maintenir au minimum le dosage de rayonnement, on utilise les isotopes de zinc possédant une courte demi-vie, tels que le zinc 62.
PCT/US2001/014664 2000-05-04 2001-05-04 Methode d'utilisation d'isotope de zinc dans la therapie et le diagnostique du cancer du colon WO2001082871A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US56691900A 2000-05-04 2000-05-04
US09/566,919 2000-05-04

Publications (2)

Publication Number Publication Date
WO2001082871A2 true WO2001082871A2 (fr) 2001-11-08
WO2001082871A3 WO2001082871A3 (fr) 2002-02-28

Family

ID=24264957

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/014664 WO2001082871A2 (fr) 2000-05-04 2001-05-04 Methode d'utilisation d'isotope de zinc dans la therapie et le diagnostique du cancer du colon

Country Status (1)

Country Link
WO (1) WO2001082871A2 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006072054A1 (fr) * 2004-12-30 2006-07-06 Genzyme Corporation Traitements a base de zinc contre l'hyperphosphatemie
US10183041B2 (en) 2017-04-12 2019-01-22 Vector Vitale Ip Llc Antibacterial composition and its use in treating bacterial infections
US10226484B2 (en) 2014-12-01 2019-03-12 Peter Y Novak Pharmaceutical composition for improving health, cure abnormalities and degenerative disease, achieve anti-aging effect of therapy and therapeutic effect on mammals and method thereof
US10799530B1 (en) 2019-12-20 2020-10-13 Vector Vitale Ip Llc Composition and method for the prevention and treatment of obesity
US10933091B1 (en) 2019-12-20 2021-03-02 Vector Vitale Ip Llc Composition and method for the treatment of type I diabetes
EP4035659A1 (fr) 2016-11-29 2022-08-03 PureTech LYT, Inc. Exosomes destinés à l'administration d'agents thérapeutiques
US11484610B2 (en) 2019-11-22 2022-11-01 Vector Vitale Ip Llc Method of treating melanoma
US11596650B2 (en) 2019-12-20 2023-03-07 Vector Vitale Ip Llc Composition and method for the treatment of type 2 diabetes

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007027566A2 (fr) 2005-09-02 2007-03-08 Genzyme Corporation Recepteurs moleculaires polymeriques utilises comme sequestrants du phosphate

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4758421A (en) * 1985-03-15 1988-07-19 The Board Of Trustees Of The Leland Stanford Junior University Bleomycin conjugates and method
US4863713A (en) * 1986-06-23 1989-09-05 The Board Of Trustees Of Leland Stanford Jr. Univ. Method and system for administering therapeutic and diagnostic agents

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4758421A (en) * 1985-03-15 1988-07-19 The Board Of Trustees Of The Leland Stanford Junior University Bleomycin conjugates and method
US4863713A (en) * 1986-06-23 1989-09-05 The Board Of Trustees Of Leland Stanford Jr. Univ. Method and system for administering therapeutic and diagnostic agents

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006072054A1 (fr) * 2004-12-30 2006-07-06 Genzyme Corporation Traitements a base de zinc contre l'hyperphosphatemie
US10226484B2 (en) 2014-12-01 2019-03-12 Peter Y Novak Pharmaceutical composition for improving health, cure abnormalities and degenerative disease, achieve anti-aging effect of therapy and therapeutic effect on mammals and method thereof
US10857180B2 (en) 2014-12-01 2020-12-08 Vector Vitale Ip Llc Pharmaceutical composition for improving health, cure abnormalities and degenerative disease, achieve anti-aging effect of therapy and therapeutic effect on mammals and method thereof
US12011458B2 (en) 2014-12-01 2024-06-18 Vector Vitale Ip Llc Pharmaceutical composition for improving health, cure abnormalities and degenerative disease, achieve anti-aging effect of therapy and therapeutic effect on mammals and method thereof
US11484550B2 (en) 2014-12-01 2022-11-01 Vector Vitale Ip Llc Pharmaceutical composition for improving health, cure abnormalities and degenerative disease, achieve anti-aging effect of therapy and therapeutic effect on mammals and method thereof
EP4035659A1 (fr) 2016-11-29 2022-08-03 PureTech LYT, Inc. Exosomes destinés à l'administration d'agents thérapeutiques
US10183041B2 (en) 2017-04-12 2019-01-22 Vector Vitale Ip Llc Antibacterial composition and its use in treating bacterial infections
US11730835B2 (en) 2019-11-22 2023-08-22 Vector Vitale Ip Llc Method of preventing the development of melanoma
US11484610B2 (en) 2019-11-22 2022-11-01 Vector Vitale Ip Llc Method of treating melanoma
US11986541B2 (en) 2019-11-22 2024-05-21 Vector Vitale Ip Llc Method of preventing the development of melanoma
US10799530B1 (en) 2019-12-20 2020-10-13 Vector Vitale Ip Llc Composition and method for the prevention and treatment of obesity
US11596650B2 (en) 2019-12-20 2023-03-07 Vector Vitale Ip Llc Composition and method for the treatment of type 2 diabetes
US10933091B1 (en) 2019-12-20 2021-03-02 Vector Vitale Ip Llc Composition and method for the treatment of type I diabetes

Also Published As

Publication number Publication date
WO2001082871A3 (fr) 2002-02-28

Similar Documents

Publication Publication Date Title
Kotb et al. Gadolinium-based nanoparticles and radiation therapy for multiple brain melanoma metastases: proof of concept before phase I trial
Taplin et al. Lung photoscans with macroaggregates of human serum radioalbumin: experimental basis and initial clinical trials
DeAngelis et al. Radiation‐induced dementia in patients cured of brain metastases
Swinney Pre-cancerous changes in bladder epithelium
Thompson et al. Prussian blue for treatment of radiocesium poisoning
Salazar et al. High dose radiation therapy in the treatment of glioblastoma multiforme: a preliminary report
Franzius et al. High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma
Kuenzle et al. Follow-up of optic pathway gliomas in children with neurofibromatosis type 1
Johnson et al. Past failures and future possibilities in Ewing's sarcoma: experimental and preliminary clinical results
WO2001082871A2 (fr) Methode d'utilisation d'isotope de zinc dans la therapie et le diagnostique du cancer du colon
EP3139967B1 (fr) Microparticules pour traitement du carcinome des cellules rénales
Medbery III et al. Pulmonary blastoma. Case report and literature review of chemotherapy experience
JP6775589B2 (ja) 骨髄抑制を治療するための薬物の製造におけるフラーレン／金属フラーレンの使用
Goldberg et al. Engraftment after myeloablative doses of 131I‐metaiodobenzylguanidine followed by autologous bone marrow transplantation for treatment of refractory neuroblastoma
Bednar et al. Primary central nervous system T-cell lymphoma: Case report
EP3946472A1 (fr) Composés de ciblage pour des cancers de l'oesophage, du pharynx et du larynx, des poumons, du cerveau ou des intestins
Ashby et al. Primary lymphoma of the central nervous system: Experience at Addenbrooke's Hospital, Cambridge
Bach et al. The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice
Watne et al. Primary malignant lymphoma of the brain: A report of 24 cases from the Norwegian Radium Hospital
Matsubara et al. A new therapeutic modality involving acridine orange excitation by photon energy used during reduction surgery for rhabdomyosarcomas
Rodger et al. Locally advanced breast cancer: report of phase II study and subsequent phase III trial
Wenliang et al. In vivo evaluation of anticancer efficacy of drug loaded cockle shell‐derived aragonite nanoparticles
Basso et al. Giant phaeochromocytoma: case report
Mir et al. Metastatic neuroblastoma after 52 years of dormancy
Taylor et al. P09. 59 Phase 2 trial of palbociclib in adult patients with recurrent Rb positive glioblastoma

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): CN JP

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR

121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): CN JP

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase in:

Ref country code: JP