54 results about "Anti mitotic" patented technology

The invention provides generally a method of monitoring, diagnosing, prognosing and treating glioma. Specifically, the invention provides for three (3) prognostic subclasses of glioma, which are differentially associated with activation of the akt and notch signaling pathways. Tumor displaying neural or proneural PN lineage markers (including notch pathway elements) show longer median patient survival, while the two remaining tumor markers Prolif and Mes are associated with shortened survival. Tumors classified in this manner may also be treated with the appropriate PN- Prolif- or Mes-therapeutic corresponding to the subclassification in combination with anti-mitotic agents, anti-angiogenic agents, Akt antagonists, and neural differentiation agents. Alternatively, the invention also provides for method of prognosing and diagnosing glioma with a two-gene model based on the expression levels of PTEN and DLL3.

Methods and compositions for the development of effective cancer therapies using mitotic inhibitors which have limited general toxicity to normal, non-cancerous cells and tissues are provided. The methods and compositions utilize cytotoxic compounds comprised of a cell-binding agent (e.g., antibodies) conjugated to an anti-mitotic compound (e.g., maytansinoids). The invention further provides antibodies which are substantially incapable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) and / or complement dependent cytotoxicity (CDC), thereby ensuring that the therapeutic effect is mediated primarily by the anti-mitotic component of the cytotoxic compound, rather than by indirect cell killing via ADCC and / or CDC. The antibodies of the invention further are capable of differentiating between polypeptide antigens which are more highly expressed on proliferating cancer cells as compared to proliferating non-cancer cells.

An implantable medical device includes a substrate, a drug-impregnated layer deposited over the substrate, and a barrier layer at least partially covering the drug-impregnated layer. The barrier layer may be a biodegradable metal, biodegradable metal oxide, or biodegradable metal alloy, such as, magnesium, a magnesium oxide or a magnesium alloy. The drug-impregnated layer includes a therapeutic substance, such as, antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, fibrinolytic, thrombin inhibitor, antimitotic, antiallergic, and antiproliferative substances.

The present invention relates to implantable medical devices, such as stents, that comprise a composition for controlled delivery of flavonoids or a derivative thereof. The flavonoids are aimed at preventing or reducing secondary complications which can occur following implantation of the device such as e.g. occlusive and catastrophic vascular phenomena. The invention further relates to the inclusion of additional therapeutic agents in the system that may have antiproliferative, antimitotic, antimicrobial, anticoagulant, fibrinolytic, anti-inflammatory, immunosurpressive, and anti-angiogenic activities. The composition comprising the flavanoids and optional further therapeutic agents may be used in methods for treating or preventing narrowing or obstruction of the body passageway. In particular the devices and compositions of the invention are useful in methods for treating or preventing restenosis, e.g. subsequent to angioplasty and / or for preventing or reducing acute, subacute and chronic secondary complications associated with angioplasty, such as e.g. thrombus.

The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.

An anti-mitotic compound with a molecular weight of at least 150 grams per mole, a mitotic index factor of at least 10 percent, a positive magnetic susceptibility of at least 1,000×10−6 cgs, and a magnetic moment of at least 0.5 bohr magnetrons. The compound contains at least 7 carbon atoms and at least one inorganic atom with a positive magnetic susceptibility of at least 200×10−6 cgs.

Compounds having cytotoxic and / or anti-mitotic activity are disclosed. The compounds have the following structure (I):including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein R1, R2, R3, R4 and R5 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having structure (I).

The present invention relates to a method of treating cancer by pretreatment with anti-mitotic agents followed by at least one aurora kinase inhibitor. Extensive illustrations are provided for the antimitotic agents and aurora kinase inhibitors that are useful in the inventive treatment.

The present invention provides substituted cyclopenta and cyclopentyl pyrimidine bicyclic compounds of Formula III,and 5,6-saturated and unsaturatedand pharmaceutically acceptable salts, prodrugs, solvates, and hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, such as for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.

The application discloses novel 2-alkoxyestradiol analogs which exhibit anti-proliferative properties, and methods of making and using such compounds to inhibit undesired cell proliferation and tumor growth. Additionally, methods are disclosed of treating diseases associated with undesired angiogenesis and undesired proliferation, and methods of treating infectious disease wherein the infectious agent is particularly susceptible to inhibition by agents that disrupt microtubule organization and function.

The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.

The invention provides generally a method of monitoring, diagnosing, prognosing and treating glioma. Specifically, the invention provides for three (3) prognostic subclasses of glioma, which are differentially associated with activation of the akt and notch signaling pathways. Tumor displaying neural or proneural PN lineage markers (including notch pathway elements) show longer median patient survival, while the two remaining tumor markers Prolif and Mes are associated with shortened survival. Tumors classified in this manner may also be treated with the appropriate PN- Prolif- or Mes- therapeutic corresponding to the subclassification in combination with anti-mitotic agents, anti-angiogenic agents, Akt antagonists, and neural differentiation agents. Alternatively, the invention also provides for method of prognosing and diagnosing glioma with a two- gene model based on the expression levels of PTEN and DLL3.

The present invention provides substituted pyrrolo-, furano-, and cyclopentylpyrimidine bicyclic compounds of formula III,and 5,6-saturated and unsaturatedand pharmaceutically acceptable salts, prodrugs, solvates, and hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, such as for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.

The application discloses novel synthetic compounds, modeled after unique toxins extracted from the marine invertebrate Diazona angulata useful in the treatment abnormal cell mitosis. The application also discloses novel methods for synthesis of these compounds and methods of using these compounds.

Methods and compositions for the development of effective cancer therapies using mitotic inhibitors which have limited general toxicity to normal, non-cancerous cells and tissues are provided. The methods and compositions utilize cytotoxic compounds comprised of a cell-binding agent (e.g., antibodies) conjugated to an anti-mitotic compound (e.g., maytansinoids). The invention further provides antibodies which are substantially incapable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) and / or complement dependent cytotoxicity (CDC), thereby ensuring that the therapeutic effect is mediated primarily by the anti-mitotic component of the cytotoxic compound, rather than by indirect cell killing via ADCC and / or CDC. The antibodies of the invention further are capable of differentiating between polypeptide antigens which are more highly expressed on proliferating cancer cells as compared to proliferating non-cancer cells.

Tubulysin compounds of the formula (I)where R1, R2R3a, R3b, R4, R5, W, and n are as defined herein, are anti-mitotic agents that can be used in the treatment of cancer, especially when conjugated to a targeting moiety.

The present invention discloses a method for high throughput screening (HTS) for identifying an analyte with a measurable effect on cells. The aforementioned method comprises steps of: (a) providing an array comprising a plurality of cell samples; (b) providing at least one analyte to be tested; (c) contacting said cell samples with said analyte; and (d) detecting a signal indicative of said measurable effect on cells wherein alteration of said signal over time measured on said cell sample relative to a control sample is indicative of said measurable effect of said analyte on said cell sample.The current invention further discloses means and methods for identifying an analyte selected from the group consisting of: cannabis extract or a fraction thereof cannabinoid- type constitute non cannabinoid-type constitute and any combination thereof. The analyte is indicative of cytotoxic or anti proliferative or anti mitotic or cell growth inhibitory activity in vitro.

The present invention relates to methods of using the compound, N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl) -1-phthalazinamine, to treat cancers, including solid tumors, which have become resistant to treatment with chemotherapeutic agents, including anti-mitotic agents such as taxanes, and / or other anti-cancer agents, including aurora kinase inhibiting agents. The invention also includes methods of treating cancers refractory to such treatments by administering a pharmaceutical composition, comprising the compound to a cancer subject.

Compounds having cytotoxic and / or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and / or anti-mitotic activity.

Methods and compositions are provided to determine if a cancer is resistant to treatment with anti-mitotic agents, including treatment with T-DM1. The methods relate to determining if the ABCC3 gene is amplified and / or overexpressed in the cancer.

The present invention refers to a combination of an eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and / or docosahexanoic acid (DHA), or a combination of a nutritional composition comprising EPA, DPA, and / or DHA and a protein, a carbohydrate, a fat, an amino acid, a fatty acid, a dietary fibre, a vitamin, a mineral, a trace element, ß-carotenoid, a flavonoid, a nucleotide, L- carnitin, choline, inositol, taurine, creatine, and / or a co-enzyme, wherein EPA is in an amount of 1 to 1000 mg / 100ml, preferably 100 to 700 mg / 100ml, DPA is in an amount of >50 mg / 100ml, preferably 50 to 1000 mg / 100ml, preferably 6 to 800 mg / 100ml, more preferably 80 to 500 mg / 100ml and / or DHA is in an amount of 1 to 500 mg / 100ml, preferably 1 to 300 mg / 100ml and a chemotherapeutic agent selected from the group consisting of an alkylating drug, an antimetabolite, an antimytotic cytostatic, a topoisomerase inhibitor, antitumor antibiotic, and any other cytostatic, and / or a radiotherapy. These combinations are successful for use in treating a neoplastic disease like the method for treating a neoplastic disease comprising EPA, DPA, and / or DHA or a nutritional composition comprising EPA, DPA, and / or DHA and and a protein, a carbohydrate, a fat, an amino acid, a fatty acid, a dietary fibre, a vitamin, a mineral, a trace element, ß-carotenoid, a flavonoid, a nucleotide, L- carnitin, choline, inositol, taurine, creatine, and / or a co-enzyme in combination with a chemotherapeutic agent, and / or radiotherapy.

Estramustine phosphate is an anti-mitotic chemotherapeutic drug with proven efficacy against cancer. The invention describes methods which potentiate the therapeutic benefit of intravenous estramustine phosphate. The invention provides for intravenous estramustine phosphate to be administered at a high dosage exceeding 1300 mg as a single dose. Efficacious enhancement of estramustine phosphate pharmacokinetics is thereby achieved. Further provided, estramustine phosphate may be intravenously administered for use in combinational regimens with other chemotherapeutic agent. The therapeutic advantages achieved using the intravenous estramustine phosphate formulation are applicable to treatment of a variety of cancers including prostate cancer, breast cancer, lung cancer, colorectal cancer, pancreatic cancer, ovarian cancer, melanoma, and other cancers.

The present invention relates to a method of treating cancer by pretreatment with anti-mitotic agents followed by at least one aurora kinase inhibitor. Extensive illustrations are provided for the antimitotic agents and aurora kinase inhibitors that are useful in the inventive treatment.

A method of screening a tumour cell for resistance to a tubulin-binding agent, the method comprising detecting the expression of any one or more of class II, class III and class IVb ss-tubulin by the tumour cell, wherein the expression of any one or more of class II, class III and class IVb ss-tubulin indicates that the tumour cell has resistance or potential resistance to the tubulin-binding agent.

Substituted triazole compounds and pharmaceutical compositions thereof are presented. Also presented are methods for treating a pathology linked to a hyperproliferative disorder by administering the substituted triazole compounds to a patient in need thereof.

Compounds having cytotoxic and / or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and / or anti-mitotic activity.

The present invention discloses a method for high throughput screening (HTS) for identifying an analyte with a measurable effect on cells. The aforementioned method comprises steps of: (a) providing an array comprising a plurality of cell samples; (b) providing at least one analyte to be tested; (c) contacting said cell samples with said analyte; and (d) detecting a signal indicative of said measurable effect on cells, wherein alteration of said signal over time measured on said cell sample relative to a control sample, is indicative of said measurable effect of said analyte on said cell sample. The current invention further discloses means and methods for identifying an analyte selected from the group consisting of: cannabis extract or a fraction thereof, cannabinoid-type constitute, non cannabinoid-type constitute and any combination thereof. The analyte is indicative of cytotoxic or anti proliferative or anti mitotic or cell growth inhibitory activity in vitro.

The present invention provides targeted polymeric nano-complexes for delivery of drugs such as anti-mitotic agents or anti-cancer agents. The present invention also provides a process for the preparation of such targeted nano-complexes.