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- Gerson, Stanton L. (x)
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Show moreField of the invention: This invention generally relates to novel compositions and methods for the treatment of certain cancers. Additionally, this invention relates to novel compositions and methods to screen drugs useful for the treatment of certain cancers. Background: Cancer is a worldwide problem. The American Cancer Society estimates that over one half million people will die from cancer in the United States alone in 1999. As such, finding novel compositions and methods for the treatment of cancer is of vital interest. The treatment of cancer falls into three general categories: chemotherapy, radiation therapy and surgery. Often, therapies are combined since a combination of therapies often increases the probability the cancer will be eradicated as compared to treatment strategies utilizing a single therapy. Most typically, the surgical excision of large tumor masses is followed by chemotherapy and/or radiation therapy. Chemotherapeutic agents can work in a number of ways. For example, chemotherapeutic can work by interfering with cell cycle progression or by generating DNA strand breaks. If the cancer cell is not able to overcome the cell cycle blockage or cell injury caused by the therapeutic compound, the cell will often die via apoptotic mechanisms. The use of a single chemotherapeutic agent in the treatment of cancer, with or without surgery or radiation, has several disadvantages. First, the cells may develop resistance to the chemotherapeutic agent. Such resistance results either in the requirement for higher dosages of the drug and/or the renewed spread of the cancer. Chemotherapeutic agents can be toxic to the patient. Therefore, there is a practical upper limit to the amount that a patient can receive. However, if two chemotherapeutic agents are used in concert, the dosage of any single drug can be lowered. This is beneficial to the patient since using lower levels of chemotherapeutic agents is generally safer for the patient. Additionally, cancer cells are less likely to generate resistance to the combination of drugs as they are to a single drug. The design of drug combinations for the chemotherapeutic treatment of cancer should be approached with the goals of 1) finding a combination that is synergistic with and not merely additive to the first compound with respect to the elimination of the tumor, and 2) finding a second drug that does not potentiate the toxic effects of the first chemotherapeutic agent. These conditions require a great deal of empirical testing of agents known to have anticancer properties with agents that either may have anticancer properties, or that may augment the first agent in other ways. TMZ is currently employed in chemotherapeutic treatment of certain tumors. It works by dramatically increasing the mutation rate of cells undergoing DNA replication.
http://www.google.com/patents?vid=USPAT6635677
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Show moreField of the invention: This invention generally relates to novel compositions and methods for the treatment of certain cancers. Additionally, this invention relates to novel compositions and methods to screen drugs useful for the treatment of certain cancers. Background: Cancer is a worldwide problem. The American Cancer Society estimates that over one half million people will die from cancer in the United States alone in 1999. As such, finding novel compositions and methods for the treatment of cancer is of vital interest. The treatment of cancer falls into three general categories: chemotherapy, radiation therapy and surgery. Often, therapies are combined since a combination of therapies often increases the probability the cancer will be eradicated as compared to treatment strategies utilizing a single therapy. Most typically, the surgical excision of large tumor masses is followed by chemotherapy and/or radiation therapy. Chemotherapeutic agents can work in a number of ways. For example, chemotherapeutic can work by interfering with cell cycle progression or by generating DNA strand breaks. If the cancer cell is not able to overcome the cell cycle blockage or cell injury caused by the therapeutic compound, the cell will often die via apoptotic mechanisms. The use of a single chemotherapeutic agent in the treatment of cancer, with or without surgery or radiation, has several disadvantages. First, the cells may develop resistance to the chemotherapeutic agent. Such resistance results either in the requirement for higher dosages of the drug and/or the renewed spread of the cancer. Chemotherapeutic agents can be toxic to the patient. Therefore, there is a practical upper limit to the amount that a patient can receive. However, if two chemotherapeutic agents are used in concert, the dosage of any single drug can be lowered. This is beneficial to the patient since using lower levels of chemotherapeutic agents is generally safer for the patient. Additionally, cancer cells are less likely to generate resistance to the combination of drugs as they are to a single drug. The design of drug combinations for the chemotherapeutic treatment of cancer should be approached with the goals of 1) finding a combination that is synergistic with and not merely additive to the first compound with respect to the elimination of the tumor, and 2) finding a second drug that does not potentiate the toxic effects of the first chemotherapeutic agent. These conditions require a great deal of empirical testing of agents known to have anticancer properties with agents that either may have anticancer properties, or that may augment the first agent in other ways. TMZ is currently employed in chemotherapeutic treatment of certain tumors. It works by dramatically increasing the mutation rate of cells undergoing DNA replication.
http://www.google.com/patents?vid=USPAT6465448
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Show moreThis invention relates to a method of screening patients undergoing drug therapy for vulnerability to drug-induced agranulocytosis. More particularly, it relates to a screening method for detecting the vulnerability of patients on clozapine therapy to developing agranulocytosis which comprises establishing the concentration of N-desmethylclozapine in the blood or bone marrow of said patients. Background of the invention: Agranulocytosis is an infrequent but potentially fatal complication associated with certain drugs that otherwise have less serious side effects and ordinarily are harmless to most patients. The complication is characterized by leukopenia (white blood count less than 2000/cu.mm.), a total absence of polymorphonuclear leukocytes (defined as less than 500/cu.mm.) and relative lymphopenia. If the disorder goes unrecognized and treatment with the drug is not discontinued, agranulocytosis will run a progressive course of increasing severity culminating in death from infection. If treatment with the drug is discontinued, complete recovery usually occurs. The period of greatest risk of agranulocytosis developing is in the first 3 to 12 weeks of treatment. Antipsychotic drugs such as neuroleptics, tricyclic antidepressants and the benzodiazepines have been implicated in producing agranulocytosis. The most significant of these is the atypical neuroleptic drug, clozapine, whose chemical name is 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e]-[1,4]diazepine. Clinical studies have shown that clozapine is effective as an antipsychotic agent in patients who are refractory and/or intolerant to classical antipsychotic drug treatment. The compound was found to be superior to standard neuroleptics; and approximately 30% of the patients conservatively defined as being refractory to these neuroleptics significantly improved with clozapine treatment. At the same time, it was found that clozapine does not cause parkinsonism or tardive dyskinesia to the same extent as classical neuroleptics and that it does not elevate prolactin secretion. With regard to tardive dyskinesia, long term treatment with clozapine appears to have a therapeutic effect against this neuroleptic side-effect, particularly the more severe form, tardive dystonia. Despite its advantages, development of clozapine has been hampered by the apparent increased risk of agranuylocytosis. Based on clinical data, the incidence in patients treated for 52 weeks with clozapine is approximately 2%. Because of this risk, patients on a clozapine regimen have to be monitored continually for hematological signs of agranulocytosis onset. A simple screening procedure which reduced or eliminated the hematological monitoring required in clozapine therapy would be highly desirable in view of the considerable therapeutic potential of clozapine for patients who are unresponsive to or intolerant of the standard neuroleptic drugs.
http://www.google.com/patents?vid=USPAT5300422
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Show moreThe present invention is directed to a totally unexplored application of human stem cells, i.e. that of genetically engineered cell that carry within them genes of interest particularly for the expression of physiologically or pharmacologically active proteins or for use in gene therapy. In accordance with the present invention it has been discovered that human mesenchymal stem cells (MSCs) or human mesenchymal progenitor cells can be used as host cells for the expression of exogenous gene products. One aspect of the invention relates to the discovery and development of the technology to isolate these cells, mitotically proliferate them in cell culture and introduce them back in vivo into the same recipient. These culture-expanded cells home back to the marrow and enhance hematopoietic recovery in the marrow transplant setting. Furthermore, these cells can be manipulated for cellular therapy, e.g. expanded, purified, selected and maintained for clinical use while still mantaining their precursor phenotype. Part of this manipulation is the characterization of such cells and their cryopreservation for future use. Mesenchymal stem cells (MSCs) can be derived from marrow, periosteum, dermis and other tissues of mesodermal origin. They are the formative pluripotential blast cells that differentiate into the specific types of connective tissues (i.e. the tissues of the body that support the specialized elements; particularly adipose, areolar, osseous, cartilaginous, elastic, marrow stroma, muscle, and fibrous connective tissues) depending upon various in vivo or in vitro environmental influences. Although these cells are normally present at very low frequencies in bone marrow, the inventors of the present invention have discovered a process for isolating, purifying, and greatly replicating the marrow-derived mesenchymal stems cells in culture, i.e. in vitro. This discovery is the subject of U.S. patents and co-pending applications, for example, Caplan and Haynesworth, U.S. Pat. Nos. 5,197,985 and 5,226,914 and PCT Publication No. WO 92/22584 (published 23 Dec. 1992) as well as numerous literature references by Caplan and Haynesworth. Isolated human hematopoietic stem cells have also been described, for example, in Tsuksamoto et al., U.S. Pat. No. 5,061,620 (October 1991) and reviewed in Edgington, Biotechnology, 10:1099-1106 (1992) and the references cited therein. These are distinguished from MSCs by their ability to differentiate into myeloid and lymphoid blood cells. In its principal embodiment the invention relates to isolated human mesenchymal stem cells capable of expressing incorporated genetic material of interest. Human stem cells are obtained from the individual donor and rendered substantially isolated from other cells and constituitive donor proteins and other components.
http://www.google.com/patents?vid=USPAT5591625
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