Synthesis and characterization of CD133 targeted aptamer–drug conjugates for precision therapy of anaplastic thyroid cancer

This study involves a synthesis of some formazan derivatives starting from react chloro acetyl chlorid with 2-amino-4-hydroxy-6-methyl pyrimidine to gate compound (a), (a) react with hydrazine hydrate to give compound (b) also (b) react with 3-4-dimethoxy benzaldehyd to product Schiff base derivative (c) then (c) react with deferent amin derivatives to get formazan derivatives. All these compounds characterized by 13C-NMR, fourier transform infrared spectroscopy (FTIR), 1HMNR. After that, we study the biological activity for all formazan derivatives toward two different kinds of bacteria and anti-cancer.

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Genomically Driven Precision Medicine to Improve Outcomes in Anaplastic Thyroid Cancer

Journal of Oncology ◽

10.1155/2014/936285 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 15

Author(s):

Nicole Pinto ◽

Morgan Black ◽

Krupal Patel ◽

John Yoo ◽

Joe S. Mymryk ◽

...

Keyword(s):

Thyroid Cancer ◽

Surgical Resection ◽

Standard Of Care ◽

Anaplastic Thyroid Cancer ◽

Genetic Alterations ◽

The Cancer Genome Atlas ◽

Genetic Landscape ◽

Cancer Genome Atlas ◽

Well Differentiated

Thyroid cancer is an endocrine malignancy with an incidence rate that has been increasing steadily over the past 30 years. While well-differentiated subtypes have a favorable prognosis when treated with surgical resection and radioiodine, undifferentiated subtypes, such as anaplastic thyroid cancer (ATC), are far more aggressive and have a poor prognosis. Conventional therapies (surgical resection, radiation, chemotherapy, and radioiodine) have been utilized for treatment of ATC, yet these treatments have not significantly improved the overall mortality rate. As cancer is a genetic disease, genetic alterations such as mutations, fusions, activation of oncogenes, and silencing of tumor suppressors contribute to its aggressiveness. With the use of next-generation sequencing and the Cancer Genome Atlas, mutation-directed therapy is recognized as the upcoming standard of care. In this review, we highlight the known genetic landscape of ATC and the need for a comprehensive genetic characterization of this disease in order to identify additional therapeutic targets to improve patient outcomes.

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A Cell-Based Internalization and Degradation Assay with an Activatable Fluorescence–Quencher Probe as a Tool for Functional Antibody Screening

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057115588511 ◽

2015 ◽

Vol 20 (7) ◽

pp. 869-875 ◽

Cited By ~ 9

Author(s):

Yan Li ◽

Peter Corbett Liu ◽

Yang Shen ◽

Marshall D. Snavely ◽

Kaori Hiraga

Keyword(s):

Cell Surface ◽

Target Cells ◽

Receptor Endocytosis ◽

Drug Conjugates ◽

Anti Cancer ◽

A Cell ◽

Rapid Characterization ◽

Fluorescence Quencher ◽

Culture Supernatants

For the development of therapeutically potent anti-cancer antibody drugs, it is often important to identify antibodies that internalize into cells efficiently, rather than just binding to antigens on the cell surface. Such antibodies can mediate receptor endocytosis, resulting in receptor downregulation on the cell surface and potentially inhibiting receptor function and tumor growth. Also, efficient antibody internalization is a prerequisite for the delivery of cytotoxic drugs into target cells and is critical for the development of antibody–drug conjugates. Here we describe a novel activatable fluorescence–quencher pair to quantify the extent of antibody internalization and degradation in the target cells. In this assay, candidate antibodies were labeled with a fluorescent dye and a quencher. Fluorescence is inhibited outside and on the surface of cells, but activated upon endocytosis and degradation of the antibody. This assay enabled the development of a process for rapid characterization of candidate antibodies potentially in a high-throughput format. By employing an activatable secondary antibody, primary antibodies in purified form or in culture supernatants can be screened for internalization and degradation. Because purification of candidate antibodies is not required, this method represents a direct functional screen to identify antibodies that internalize efficiently early in the discovery process.

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