2,500 research outputs found

    Targeting delivery of paclitaxel into tumor cells via somatostatin receptor endocytosis

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    AbstractBackground: The binding of somatostatin (SST) to endogenous G-protein-coupled receptors (SST receptors or SSTRs) is followed by internalization of SST, and, several reports have shown that a high density of SSTRs is present on most hormone-secreting tissue tumors. Facile synthesis of the long-acting SST analog, octreotide, has previously been described. Octreotide might be of practical value in developing tumor tracers and in serving as a carrier of cytotoxic antitumor drugs.Results: Fluorescein-labeled octreotide was internalized into the cytosol of human breast MCF-7 carcinoma cells via binding to SSTRs. Octreotide-conjugated paclitaxel (taxol) was created by coupling taxol–succinate to the amino-terminal end of octreotide. This conjugate retains the biological activity of taxol in inducing formation of tubulin bundles, eventually causing apoptosis of MCF-7 cells. Cytotoxicity of octreotide-conjugated taxol is mainly mediated by SSTR, as shown by the observation that octreotide pretreatment can rescue the induced cell death. In comparison with free taxol, this conjugate shows much less toxicity in Chinese hamster ovary cells.Conclusions: Octreotide-conjugated taxol exerts the same antitumor effect of free taxol on stabilizing microtubule formation and inducing cell death. This conjugate triggers tumor cell apoptosis mediated by SSTRs and is exclusively toxic to SSTR-expressing cells. Octreotide-conjugated taxol is less toxic to low-SSTR-expressing cells compared with free taxol. Our results strongly indicated that octreotide-conjugated taxol demonstrates cell selectivity and may be used as a targeting agent for cancer therapy

    On the Quality of Service of Cloud Gaming Systems

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    Glutamatergic Dysfunction and Glutamatergic Compounds for Major Psychiatric Disorders: Evidence From Clinical Neuroimaging Studies

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    Excessive glutamate release has been linked to stress and many neurodegenerative diseases. Evidence indicates abnormalities of glutamatergic neurotransmission or glutamatergic dysfunction as playing an important role in the development of many major psychiatric disorders (e.g., schizophrenia, bipolar disorder, and major depressive disorder). Recently, ketamine, an N-methyl-d-aspartate antagonist, has been demonstrated to have promisingly rapid antidepressant efficacy for treatment-resistant depression. Many compounds that target the glutamate system have also become available that possess potential in the treatment of major psychiatric disorders. In this review, we update evidence from recent human studies that directly or indirectly measured glutamatergic neurotransmission and function in major psychiatric disorders using modalities such as magnetic resonance spectroscopy, positron emission tomography/single-photon emission computed tomography, and paired-pulse transcranial magnetic stimulation. The newer generation of antidepressants that target the glutamatergic system developed in human clinical studies is also reviewed

    A high-speed algorithm for elliptical object detection

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