69 results about "Metastatic melanoma" patented technology

The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.

The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.

Topically applied transdermally quick penetrating (best targeting the epidermis and subsequently remaining there for a prolonged period of time) systemic independent acting, combinations and formulations which employ, combine, or incorporate a therapeutically effective non-toxic (to the patient) amount of a drug which inhibits prostaglandin synthesis together with an amount of hyaluronic acid and / or salts thereof (for example the sodium salt) and / or homologues, analogues, derivatives, complexes, esters, fragments, and / or sub units of hyaluronic acid to treat a disease and condition of the skin and exposed tissue for example, basal cell carcinoma, the precancerous, often recurrent, actinic keratoses lesions, fungal lesions, "liver" spots and like lesions (found for the most part in the epidermis), squamous cell tumours, metastatic cancer of the breast to the skin, primary and metastatic melanoma in the skin, genital warts cervical cancer, and HPV (Human Papilloma Virus) including HPV of the cervix, psoriasis (both plaque-type psoriasis and nail bed psoriasis), corns on the feet and hair loss on the head of pregnant women and remain in the skin for a prolonged period of time.

The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.

Autotaxin (ATX) is a prometastatic enzyme initially isolated from the conditioned media of human melanoma cells that stimulates a myriad of biological activities including angiogenesis and the promotion of cell growth, survival, and differentiation through the production of lysophosphatidic acid (LPA). ATX increases the aggressiveness and invasiveness of transformed cells, and ATX levels directly correlate with tumor stage and grade in several human malignancies. To study the role of ATX in the pathogenesis of malignant melanoma, we developed antibodies and small molecule inhibitors against recombinant human protein. Immunohistochemistry of paraffin embedded human tissue demonstrates that ATX levels are markedly increased in human primary and metastatic melanoma relative to benign nevi. Chemical screens identified several small molecule inhibitors with binding constants ranging from nanomolar to low micromolar. Cell migration and invasion assays with melanoma cell lines demonstrate that ATX markedly stimulates melanoma cell migration and invasion, an effect suppressed by ATX inhibitors. The migratory phenotype can be rescued by the addition of ATX's enzymatic product, LPA, confirming that the observed inhibition is linked to suppression of LPA production by ATX. Chemical analogues of the inhibitors demonstrate structure activity relationships important for ATX inhibition and indicate pathways for their optimization. These studies suggest that ATX is an approachable molecular target for the rational design of chemotherapeutic agents directed against human malignancies driven by the ATX / LPA axis, especially including malignant melanoma, among numerous others including breast and ovarian cancers.

The invention provides a quantitative realtime RT-PCR assay for detection of metastatic breast, gastric, pancreas or colon cancer cells or metastatic melanoma. The assay allows to predict disease recurrence and survival in patients with AJCC stage I and II, and III disease using multimarker panels. The method for detecting metastatic melanoma cells utilizes panels of markers selected from a group consisting of MAGE-A3, GalNAcT, MART-1, PAX3, Mitf, TRP-2, and Tyrosinase. The method for detecting metastatic breast, gastric, pancreas or colon cancer cells in paraffin-embedded samples utilizes panels of markers selected from a group consisting of C-Met, MAGE-A3, Stanniocalcin-1, mammoglobin, HSP27, GalNAcT, CK20, and β-HCG.

Embodiments of methods and apparatus use electron paramagnetic resonance spectroscopy to provide a signal from melanin to image a melanoma. Embodiments of methods and apparatus use electron paramagnetic resonance spectroscopy to provide a signal from melanin to detect metastatic melanoma in a sentinel lymph node. Embodiments of methods and apparatus use electron paramagnetic resonance spectroscopy to provide a signal from melanin to measure light penetration in melanocytes in skin.

A method for the treatment of cancer, particularly a metastatic melanoma or a neoplastic lesion, the method comprising intralesional administration of a hydrophilic vehicle comprising 4,5,6,7-Tetrachloro-2′,4′,5′,7′-tetraiodofluorescein, or a physiologically acceptable salt thereof, at a concentration of about 0.1 w / v % up to about 20 w / v % and an electrolyte comprising at least one cation selected from the group consisting of sodium, potassium, calcium and magnesium and at least one anion selected from the group consisting of chlorine, a phosphate and a nitrate, wherein the electrolyte is at a concentration of between about 0.1 w / v % and about 2 w / v % and the pH of the solution between about 4 to about 10.

The invention discloses a completely humanized anti-VEGFR-2 monoclonal antibody, and discloses a method of screening by adopting a phage antibody library technique and preparing the novel anti-VEGFR-2 monoclonal antibody or a segment thereof by utilizing a genetic engineering manner. The antibody can be a univalent antibody or a bivalent antibody. The antibody can interdict VEGF-A, VEGF-C, VEGF-D and VEGF-E simultaneously so that the antibody has more effective anti-angiogenesis effects. The antibody can be applied for treating diseases caused by tumor angiogenesis. The diseases comprise, but not limited to, gastric cancer, adenocarcinoma of esophagogastric junction, non-small cell lung cancer, metastatic non-small cell lung cancer, hepatocellular carcinoma, metastatic hepatocellular carcinoma, HER2-negtive metastatic breast cancer, metastatic colorectal cancer, metastatic melanoma, metastatic renal cell carcinoma, glioblastoma, ovarian cancer, prostate cancer and solid tumor.

The present invention relates to methods of treating patients with advanced forms of cancer, such as metastatic melanoma and non-small cell lung cancer, in which X4P-001 is administered as monotherapy or in combination with immune checkpoint inhibitors, such as pembrolizumab. The methods demonstrate surprising results, including regression of disease, with comparatively little toxicity.

The invention provides a quantitative realtime RT-PCR assay for detection of metastatic breast, gastric, pancreas or colon cancer cells or metastatic melanoma. The assay allows to predict disease recurrence and survival in patients with AJCC stage I and II, and III disease using multimarker panels. The method for detecting metastatic melanoma cells utilizes panels of markers selected from a group consisting of MAGE-A3, GalNAcT, MART-1, PAX3, Mitf, TRP-2, and Tyrosinase. The method for detecting metastatic breast, gastric, pancreas or colon cancer cells in paraffin-embedded samples utilizes panels of markers selected from a group consisting of C-Met, MAGE-A3, Stanniocalcin-1, mammoglobin, HSP27, GalNAcT, CK20, and beta-HCG.

The present invention is directed to novel non-invasive diagnostic tools / compounds comprising a cyclic peptide wherein the compound binds to a MSH receptor to image and treat cancers, especially, melanoma, including metastatic melanoma in vivo. The present invention represents a clear advance in the art which presently relies on tissue biopsy for diagnoses of these cancers. The novel imaging probes are capable of detecting cancerous melanoma cells, as well as their metastatic spread in tissues. The present invention represents a step forward in the diagnosis and treatment of melanoma, including metastatic melanoma using non-invasive molecular imaging techniques. The novel probes of the present invention are also useful to initiate therapy for melanoma as well as monitor patients response to chemotherapy treatments and other interventions or therapies used in the treatment of melanoma / metastatic melanoma. Compounds according to the present invention may be used as diagnostic tools for a number of conditions and diseases states as well as therapeutic agents for treating such conditions and disease states.

The present invention relates to methods for predicting and evaluating metastasis of solid cancers, such as melanoma, in a subject by measuring serum biomarkers associated with a metastatic phenotype. In particular, the present invention provides a serum gene expression signature that is different between highly aggressive and more metastatic versus less aggressive and less metastatic melanomas by quantitatively measuring the levels of, inter alia, lymphoid-specific helicase (HELLS) and condensing complex subunit 2 (NCAPH) transcripts in a subject.

The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.

The invention discloses a highly metastatic model of human melanoma, a highly metastatic cell subline of the human melanoma, creation methods for the highly metastatic model and the highly metastatic cell subline, and the dynamic detection of metastasis. The subcutaneously-transplanted mouse highly metastatic model and the corresponding cell subline are established in an in-vivo screening way in a mouse with severe combined immune deficiency (SCID) by using mouse lung metastasis, namely human malignant melanoma cell strain A375 pulmonary metastasis, wherein the highly metastatic cell subline of the human melanoma is A375sci, and has a human tumor cell karyotype; and 60 to 75 hypo-triploid-dominated chromosomes are acrocentric and have a heteroploid karyotype. The cell subline has the two routes of metastasis of blood trails and lymph. The in-vivo screening of the highly-metastatic model is performed by using animals with severe immune deficiency, and is expressed and applied in nude mice. A method for detecting Alu genes by using a polymerase chain reaction (PCR) method is simple, highly sensitive and highly specific, and can be used for detecting organ metastasis, particularly micrometastasis, in a human tumor animal-xenotransplantation model.

The present invention is directed to novel non-invasive diagnostic tools / compounds to image cancers, especially, melanoma, including metastatic melanoma in vivo. The present compounds exhibit enhanced uptake in cancerous cells and tissue and decreased renal uptake in kidney, evidencing favorable pharmacokinetics of compounds of the present invention. The compounds according to the present invention represent an advance in the diagnosis and treatment of melanoma, including metastatic melanoma using non-invasive molecular imaging techniques. The novel probes of the present invention are also useful for initiating therapy for melanoma as well as monitor patients' response to chemotherapy treatments and other interventions or therapies used in the treatment of melanoma / metastatic melanoma. Compounds according to the present invention may be used as diagnostic tools for a number of conditions and diseases states as well as therapeutic agents for treating such conditions and disease states.

Cellular and genetic signatures and methods of using same for subcategorizing stage III melanoma tumors are described herein. The signatures and methods are particularly useful with regard to establishing more distinct criteria on which basis to differentiate stage IIIB and IIIC melanoma patients. Assessment of the cellular and genetic signatures of a melanoma sample using methods described herein yields information on which basis differential survival duration and sensitivity to various cancer therapies can be predicted for a Stage IIIB or Stage IIIC melanoma patients. As described herein, gene expression profiling, determination of mitotic index (MI), and quantification of tumor infiltrating leukocytes (TILs) and CD3+ cells in metastatic lesions may be utilized to predict or assess drug response, drug sensitivity, and clinical outcome in metastatic melanoma patients.

The present invention relates to combination therapies for melanoma, and in particular, metastatic melanoma. Drugs for use in such therapies in include MEK inhibitors combination with cardiac glycosides.

The present invention is directed to novel non-invasive diagnostic and therapeutic tools / compounds comprising a hybride cyclic peptide which utilizes a cyclic peptide chelating group wherein the compound binds to a MSH receptor to image and treat cancers, especially, melanoma, including metastatic melanoma in vivo. The present invention represents a clear advance in the art which presently relies on tissue biopsy for diagnoses of these cancers. The novel imaging probes are capable of detecting cancerous melanoma cells, as well as their metastatic spread in tissues. This represents a quantum step forward in the diagnosis and treatment of melanoma, including metastatic melanoma using non-invasive molecular imaging techniques. The novel probes of the present invention will also be useful to initiate therapy for melanoma as well as monitor patients response to chemotherapy treatments and other interventions or therapies used in the treatment of melanoma / metastatic melanoma. Compound according to the present invention may be used as diagnostic tools for a number of conditions and diseases states as well as therapeutic agents for treating such conditions and disease states.

Methods of inhibiting melanoma tumor growth, methods of treating melanoma and metastatic melanoma, and methods of reducing the frequency of tumor initiating cells (or cancer stem cells) in melanoma tumors are described. The methods described comprise administering a DLL4 antagonist (e.g., an antibody that specifically binds the extracellular domain of human DLL4) to a subject. Related polypeptides and polynucleotides, compositions comprising the DLL4 antagonists, and methods of making the DLL4 antagonists are also described.

The present invention provides methods for use of IL-21 in combination with a tyrosine kinase inhibitor (TKI) in treatment of diseases in which inhibition of phosphorylation via TK inhibition and modulation of immune function play a clinically beneficial role. These diseases include, but are not limited to, cancers, such as renal cell carcinoma and metastatic melanoma.

The present invention includes compositions, systems and methods for the early detection and consistent determination of metastatic melanoma and / or immunosuppression using microarrays by calculating one or more expression vectors from the expression of one or more genes.

The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.

There is provided a method for inhibiting ATF / CREB and cancer cell growth using disulfiram, administered in combination with heavy metals. It was found that disulfiram disrupts transcription factor DNA binding by forming mixed disulfides with thiols within the DNA-binding region, and that this process is facilitated by metal ions. Disulfiram administered to melanoma cells in combination with copper (II) or zinc(II) decreased expression of cyclin A, reduced proliferation in vitro, and inhibited growth of melanoma cells. The combination of oral zinc gluconate and disulfiram at currently approved doses for alcoholism stabilized tumor growth in two of three patients with Stage IV metastatic melanoma, with 12 and 17 month survivals, respectively, to date, and produced a >50% reduction in hepatic metastases in one individual.

The present invention relates to a crystal form B of ABT-888, a preparation method and applications thereof, wherein the characteristic peaks exist in the X-ray powder diffraction spectrum (CuK[alpha] radiation) of the crystal form B when the 2[theta] value is 9.4+ / -0.2 DEG, 17.3+ / -0.2 DEG, and 22.8+ / -0.2 DEG. The preparation method comprises: dissolving ABT-888 free alkali in methanol, and naturally volatilizing at a room temperature to obtain the crystal form B. Compared with the existing crystal form, the crystal form B has characteristics of high solubility, simple preparation process and good stability, and provides important significance for improvement of treatment effects of metastatic breast cancer, colon cancer, metastatic melanoma and brain tumor and reduction of drug loading.

The invention discloses a monoclonal antibody or sections thereof, which is sieved by utilizing a bacteriophage antibody database technology and prepared by utilizing a gene engineering method, of VEGFR2, and also discloses a carrier containing polynucleotide, which codes the monoclonal antibody or sections thereof, host cells, a method of preparing and purifying, and applications. The monoclonal antibody or sections thereof is used for preparing medicines for curing diseases caused by cancer new-born blood vessels. The diseases contain but not limited to following cancers: non-small cell lung cancer, metastatic non-small-cell lung cancer, hepatocellular carcinoma, metastatic hepatocellular carcinoma, HER2 negative metastatic breast cancer, metastatic gastric gland cancer, metastatic colorectal cancer, metastatic melanoma, and metastatic renal cell carcinoma.

Provided are SLC45A2 peptides that bind to MHC I (HLA-A2) on melanoma cells or other antigen-presenting cells and are recognized by T-cell receptors on T cells. The SLC45 A2 peptides may be therapeutically used to treat a cancer, such as a cutaneous melanoma, uveal melanoma, a mucosal melanoma, or a metastatic melanoma. Methods for expanding a population of T cells that target SLC45A2 are also provided.