The invention relates to cyclic peptide agonists that bind to the mu (morphine) opioid receptor and their use in the treatment of acute and/or chronic pain. Embodiments of the invention are directed to cyclic pentapeptide and hexapeptide analogs of endomorphin that have (i) a carboxy-terminal extension with an amidated hydrophilic amino acid and (ii) a substitution in amino acid position 2, and in some embodiments, a 2′,6′-dimethyltyrosine (Dmt) residue in place of the N-terminal tyrosine residue a position 1. These peptide analogs exhibit increased solubility compared to similar tetrapeptide analogs while maintaining favorable or improved therapeutic ratios of analgesia to side effects.

A method of identifying a potential therapeutic compound that affects a Receptor Tyrosine Kinase (RTK) pathway in cancer cells, which includes: providing a device capable of measuring cell-substrate impedance; culturing cancer cells in serum-free media in at least two wells of the device; adding to a first well a proposed therapeutic compound that affects a RTK pathway and a RTK stimulating factor for the RTK pathway to form a test well, and adding to another well the RTK stimulating factor to form a control well; continuously monitoring cell-substrate impedance of the at least two wells and optionally determining cell indices from the monitored cell-substrate impedance; and determining a difference in impedance or optionally cell index between the test well and control well; and if significantly different, concluding the proposed therapeutic compound is therapeutically active in the RTK pathway within the cancer cells.

The present technology is directed to compounds, compositions, medicaments, and methods related to the treatment of cancers expressing PSMA. The compounds are of Formulas I & II

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or pharmaceutically acceptable salts thereof. The present technology is especially well-suited for use in treating prostate cancer.

The present invention relates to methods for treating an individual with high grade glioblastoma multiforme by preventing or disrupting the binding of CD95 to its ligand, CD95L, in vivo, whereupon that neutralization of CD95 activity reduces undesirable glial cell migration and invasion into body tissue.

The present Inventors demonstrated that the RelB subunit of NFκB plays a crucial role in promoting cell migration. More precisely, they identified that this pro-migratory activity is mediated by the activation of the NFκB pathway through RelB phosphorylation at serine 472. In a first aspect, the present invention proposes to monitor the activation of the NFκB pathway by following the phosphorylation status of said serine. Also, the present invention discloses methods and kits for prognosing the evolution of a disease involving cell migration in a subject—treated or not—suffering thereof, based on the detection of said RelB-S472 phosphorylation.

The present invention encompasses the recognition that identification of alternative means to block RAS oncogenic signaling may be required for developing novel cancer therapies. Among other things, the present invention encompasses the recognition that targeting RAS palmitoylation can achieve effective therapy for RAS-related cancers. Furthermore, the present invention encompasses the recognition that reduction of ZDHHC9 level and/or activity can significantly reduce palmitoylation level of Ras protein. Among other things, the present invention encompasses the recognition that identification of agents that modulate expression and/or activity of ZDHHC9 can reduce palmitoylation level of Ras protein. In some embodiments, the present invention provides methods of treating a subject suffering from cancer by administering ZDHHC9 inhibition therapy.

The invention relates to cyclic peptide agonists that bind to the mu (morphine) opioid receptor and their use in the treatment of acute and/or chronic pain. Embodiments of the invention are directed to cyclic analogs of endomorphin. These peptide analogs exhibit decreased tolerance relative to morphine, increased solubility compared to similar tetrapeptide analogs, while maintaining favorable or improved therapeutic ratios of analgesia to side effects.

An observation method of a sample containing a target substance, the observation method including an imaging step in which a step of obtaining a speckle image including, as a speckle, light emitted from a luminescent substance in which a medium is brought into contact with the sample is performed a plurality of times so as to obtain a plurality of speckle images, the medium containing a probe that contains the luminescent substance emitting light and that repeatedly binds to and dissociates from the target substance directly and specifically, and an observation image generation step of generating an observation image of the target substance in the sample from the plurality of speckle images, wherein a half-life of a probe-target complex formed by binding between the probe and the target substance is equal to or more than 10 milliseconds and equal to or less than 3 seconds.

It has been revealed that, from a pre-onset stage of Alzheimer's disease, enhancement of phosphorylations of MARCKS and the like causes abnormal spine formation or the like, consequently developing the disease. It also has been revealed that the phosphorylations of MARCKS and the like are caused by PKC and the like, and further that b-raf is involved in phosphorylation of tau protein important for the progression of Alzheimer's disease. Thus, these proteins have been found to be target molecules useful in the diagnosis and treatment of Alzheimer's disease. In addition, it has also been revealed that, in a pre-onset stage of frontotemporal lobar degeneration, b-RAF phosphorylation enhancement causes a decrease in the number of spines and the like, consequently developing the disease. Thus, b-RAF has been found to be a target molecule useful in the diagnosis and treatment of frontotemporal lobar degeneration.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.