P01 meetings. Every Friday at 10 a.m. B180 Med Labs

October 5—Introduction to the P01 and overall goal.

October 12—Spitz lab. Iron studies and immunological studies in lung clinical trial

October19—Cullen lab. Pharmacological ascorbate as a radiosensitizer in pancreatic cancer.

October 26—Discussion regarding 15 g Ascorbate test dose. Update on GBM trial and Spitz lab grad student discussion of NAD metabolism in cancer.

November 2—Colin Heer presenting on NAD metabolism.

November 9—Cullen lab presenting new techniques to measure circulating tumor cells. Cullen lab also presenting new techniques to measure ascorbate responses to tumor spheres and oxidation of patient samples from clinical trials.

November 16—Off due to SFRBM

November 23—Off due to Thanksgiving break

November 30—Visarut Buranasudja presenting on DNA damage and disruption of cellular bioenergetics contribute to the anti-cancer effects of pharmacological ascorbate

December 7—Cam Cushing. Measuring iron levels using MRI in GBM following P-ascorbate and radiation. Mike Petronek—Measuring iron levels in orthotopic models of GBM

December 14—Clinical trials core. Kellie Bodeker discussed clinical trials, regulations, FDA and IRB regulations.

December 21—off for holiday

December 28—off for holiday


January 4—Project 2. Doug Spitz and Colin Heer spoke about combining the SOD mimetic GC4419 combined with pharmacological ascorbate. Also discussion of new Small Animal Radiation platform.

January 11—Project 1. Cameron Callaghan (Holman pathway resident) presented combination of pharmacological ascorbate with radiotherapy, and addition of ATM and ATR inhibitors.

January 18—Project 3. Translational meeting, hiring and finances. Imaging needs in Project 2. Scientific discussion on MRI-T2* mapping in pharmacological ascorbate and glioblastoma. Discussion of insurance coverage of imaging during treatment.

January 25—Administrative Core. Only Project leaders involved. Discussion included budget and possible additional nursing or research personnel.

February 1—break

February 8—Biomarkers core. Garry Buettner discussed mechanisms and resources available to all P01 members for measuring redox metabolism and measurement of ascorbate levels in all of the clinical trials.

February 15—Clinical trials core. Discussion need for blood draws and measurement of GSH/GSSG in blood and serum in the clinical trials. In addition, correlation with ROS measurements with PET scans. Project 2 clinical trial creatinine levels and re-evaluation of the protocol. Discussion centered on current accrual in all the clinical trials for Projects 1-3.

February 22—Project 2. NAMPT inhibitors combined with standard of care chemotherapy in NSCLC. Repurposing Disulfiram and copper metabolism in cancer. FLASH radiation changes in metabolism.

March 1—Project 1. Discussed different approaches to investigate P-AscH- inhibition of metastatic disease in pancreatic cancer. Discussed recent data demonstrating P-AscH- pretreatment vs. posttreatment, following splenic injections.

March 8—Discussion of clinical trials and BEACON in the electronic medical record.

March 15—start of spring break

March 22—Spring break

March 29—Project 3. MRI based T2* mapping in orthotopic murine gliomas as a method of probing iron metabolism in vivo. T2* mapping in patients receiving P-AscH and chemoradiation for glioblastomas.

April 5—Discussed dose modification for PACMAN 2.1 regarding dosing of gemcitabine + Abraxane.

April 19—Clinical trials Core C update. Discussion of xACT lung trial and use of PET CT scan in demonstrating metastatic disease. Already have 7 patients enrolled in this trial. Current accruals were examined. All trials are accruing at an acceptable rate except for PACMAN 2.1. This trial has enrolled 2 and should be at 7.5. Discussed ways to increase accrual including adding Henry Ford and Penn State as enrolling sites. The two new sites will be under the University of Iowa IRB which is a first for the UI.  Discuss Dan Xi email. “As we discussed in Dec web meeting, if you need additional funds to screen additional molecular signatures of the tumor or treatment, e.g. Kras/Braf , IDH1 or epigenome, please write the budget request and justification.  I will try to make the request from NCI for the possibility of adding additional funds.”

April 26—No meeting due to out of town absences

May 3—Doug Spitz speaking about Flash irradiation. Potential benefits due to fundamental metabolism between normal and tumor cells.

May 10—Discussed date and program for external advisers in the fall.

May 31–Discussion of lente virus transfected cell lines (small cell lung, pancreatic, lung and brain with mitochondrial-targeted catalase, light and heavy ferritin) and the design of a mouse experiment combining ascorbate with small molecule superoxide scavenger GC, in small cell lung cancer.

June 7—Project 3, Allen group. T2* mapping of orthotopic mouse gliomas as an in vivo method of probing tumor iron metabolism. Announced and discussed external advisors meeting will be October 30-31 which includes Dr. Wicha (University of Michigan) and Dr. Hauer-Jensen (University of Arkansas).

June 14—Discussion of budget and renewal and progress report for the P01. Also discussed plans for the external advisor meeting.

June 28—Presentation by new Immunology group and immunology core in the Cancer Center. Presentation of immunological studies (CD8 t cells) in lung cancer patients (xACT lung cancer trial, Project 2) receiving pharmacological ascorbate. Discussion of amendments to protocols, specifically at other sites other than UIHC.

July 5—Off due to holiday absences.

July 12—Jessica Sieren, Ph.D., Department of Radiology. Post-imaging mathematical prediction models that are clinically relevant. Approach to transferrin in tumors in regards to P-AscH treatments for Project #2.

July 26– Reviewed and finalized the blood sample processing/shipping communication document for Henry Ford Hospital System as a secondary site for PACMAN 2.1 (project 1) and Xact Lung (project 2).

September 6—Project 3, Current imaging results. Quantitative imaging in glioblastoma with pharmacological ascorbate therapy.

September 20—Project 1. Role of P-AscH inducible Dual Oxidase 1 and 2 in pancreatic cancer. Discussed workflow issues with changing personnel and ordering equipment.

September 27—Project 2.  Discussed preliminary studies investigating ATM and ATR inhibitors in colon cancer when combined with radiation and pharmacological ascorbate. Dr. Furquan discussed pulmonary injury and other normal tissue toxicity with immunologic therapy for lung cancer.

October 4—Discussion of schedule for external advisers on October 30-31.

October 25—Preparation for external advisers meeting.