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2007 Annual Report

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Chromosome Changes =

Chromosome Changes = Changes in Tumor Type >> Changes in the chromosomal content (e.g., number of copies of each chromosome) of tumor cells occur when the cell switches from a type that simply multiplies to one that aggressively spreads. (Vande Woude Lab - Proceedings of the National Academy of Sciences U.S.A.) Insights into Cell Movement >> The “skeletons” of cells change to facilitate several different processes. The dynamics of these structures, controlled by the protein mDia2, contribute to the movement of vesicles (storage and transportation vehicles) within the cell. (Alberts Lab - Experimental Cell Research) >> While prostate cancer cells need the enzyme PI-3K to survive, normal prostate cells do not. (Miranti Lab - Molecular Biology of the Cell) “Our study confirms the therapeutic potential; PI-3K is important because we now know that therapeutics that target this enzyme could kill tumor cells without having a negative effect on normal cells.” —Cindy Miranti, Ph.D., Scientific Investigator >> Naturally occurring cellular protein DIP can trigger “blebbing” – cell bubbling that has recently been linked to the development of secondary tumors away from the primary cancer site. (Alberts Lab - Current Biology) “We now have a mechanism that we can target with drugs aimed at interfering with cancer metastasis; currently, no anti-cancer therapies block this critical step in the malignancy process.” —Art Alberts, Ph.D., Senior Scientific Investigator Diagnostic Discoveries >> A potential biomarker for prostate cancer could help avoid unnecessary biopsies: thrombospondin-1. Higher levels of this protein are found in patients with benign prostatic disease; the opposite is true for patients with prostate cancer. (Haab Lab - The Prostate) Van Andel Research Institute

Two different categories of blood vessels in clear cell renal cell carcinoma (CCRCC) tumors correlate with contrasting prognoses; more of one vessel type is associated with higher tumor grades and shorter patient survival, while more of the other vessel type correlates with lower tumor grades and longer survival. This information could be used to help diagnose and even determine optimal treatment for patients based on what type of blood vessels their tumors have. (Teh Lab - Clinical Cancer Research) - - Tumors need access to blood vessels for nutrients and other essentials to survive and grow. >> A new method to profile cancer biomarkers for intestinal tumors can help distinguish normal blood from that of genetic models predisposed to intestinal cancer based on the levels of as few as three markers, even when the predisposed models have no tumors yet. (Haab Lab - Molecular Oncology) - - A biomarker is something in the body that can be associated with disease to help predict, diagnose, or determine optimal treatment. >> A new strategy to screen for, identify, and validate proteins from tumors that trigger immune responses (tumor antigens) identified the protein human Kallikrein 11 as one such protein in prostate cancer and profiled its immune response. (Haab Lab - Proteomics – Clinical Applications) >> “Switching off” the tumor suppressor gene Pten could increase bone density in osteoporosis patients and people with bone fractures, probably by allowing osteoblast cells to live longer and make more bone cells. (Williams Lab - Proceedings of the National Academy of Sciences U.S.A.) VARI Lab Potential for Treatment >> The growth of tumor cells having high levels of epidermal growth factor receptor (EGFR) is slowed when treated with an anti-EGFR antibody that researchers developed and attached to the chemotherapeutic drug Taxol. This combination could have potential for clinical treatment of tumors having high levels of EGFR. (Cao Lab - Cancer Biology & Therapy) “We were discussing what could be involved in helping bone cells survive longer with our collaborations at the University of Alabama and our work suggested that Pten might be important. Now the trick is to turn off Pten only in bone-making osteoblasts without affecting other cells.” Highlights 2007 —Bart WIlliams, Ph.D., Senior Scientific Investigator www.vai.org 11

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2020 Convocation: New Graduate Student Bios