68 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.

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.

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 beta-HCG.

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.