Bound Volume Number

Volume III

Degree Type

Honors Capstone Project

Capstone Advisor

Thomas Fondy

Capstone Major


Capstone College

Arts and Science

Audio/Visual Component



Low frequency ultrasound, mTOR, Rapamycin, Everolimus, Temsirolimus, Human Leukemia

Capstone Prize Winner


Won Capstone Funding


Honors Categories

Sciences and Engineering

Subject Categories



It has been shown that the mammalian target of rapamycin (mTOR) pathway, which regulates cell growth and proliferation, is aberrant in many hematological malignancies. Rapamycin inhibits mTOR signaling which regulates cell growth and cell cycle progression. This study sought to determine the effects of mTOR inhibitors on the cell sizes of normal and neoplastic cells and to determine ultrasonic sensitivity of normal and neoplastic cells treated with mTOR inhibitors. The effects of rapamycin (rapa), an extensively studied natural product that affects cell cycle entry by inhibiting mTORC1, and its analogs temsirolimus (tems) and everolimus (eve), were examined on leukemic cell lines (U937: Human monocytic leukemia, THP-1: Human acute monocytic lymphoma, K562: Human chronic myelogenous leukemia, and MOLT-4, Human acute lymphoblastic leukemia) in combination with 20kHz ultrasound. Each cell line was treated for 48 hours with each analog before being exposed to ultrasound. By using low frequency ultrasound of 5 pulses (0.6 seconds of ultrasound and 0.4 seconds without ultrasound) at 20 kHz and 30% amplitude (60W), we determined that as the concentrations of Rapa, Eve, and Tems (2, 20, and 50nM) increased, there is usually the most sonic damage observed in U937, MOLT-4, K562, and THP-1 cells. The most preferentially damaged cell line is K562 by all of the analogs and with all the concentrations used. In addition, larger cells were more susceptible to ultrasonic damage than were smaller cells. Further, there are no significant differences among the three analogs in the potentiation of ultrasonic damage. This preliminary therapeutic approach involving the use of ultra-sound in combination with mTOR inhibitors might eventually provide an improved approach to the treatment of leukemia and other hematological malignancies in a clinical setting.

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

Included in

Biotechnology Commons



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.