Month: May 2003

UNC

I have an appointment at UNC with Dr. Orlowski on June 11th at 8:30 am. I’m glad that’s been rescheduled and look forward to having someone knowledgable about MM to work with who’s closer than Boston. Dr. Richardson at Dana-Farber worked with Dr. Orlowski on a clinical trial before – Velcade, I think. I believe in one of the early phases.

Hard sell

If you ever watched one of those Craftmatic adjustable bed commercials and thought they looked cool, but wondered how much they cost, I can tell you. I went to their web site, looking for prices, and found none. I submitted my contact info online, and asked for pricing. Here’s what happened. One of the Craftmatic telemarketing reps called to set up an appointment for me to see a sales rep. They don’t give you any prices over the phone (or on the web, or on TV). I think I know why. The model I costs over $4,000. I think most of us would immediately lose interest. I’m sure it’s a really nice bed. Afterall, it does have a massage feature, and is adjustable for legs and upper body. I don’t know about spending that much money without even getting to try the thing out though. It’d almost be like buying a car you didn’t get to test drive. Anyway, after seeing the sales presentation, there really was a high pressure effort made to get me to put some money down on one of the beds. There were calls made back to headquarters, even! Could I write a check? Use a credit card? Do I need financing? After an hour and 45 minutes, the effort drew to a close. I guess I should have known!

Acupuncture

I had an acupuncture session yesterday afternoon. It does help me feel better. It’s very relaxing, and does alleviate some of my back pain. I fall asleep sometimes while I’m there. The acupuncturist says that endorphins are released and that’s why I feel so relaxed. Since I’ll be in Boston next week, I’ll skip a week and then continue to go weekly.

Appointments

2004 Toyota SiennaI had an appointment with my Pinehurst oncologist this morning. I called in to say I wouldn’t make it, and they gave me a later appointment time. I’ll be seeing Dr. R. in Boston in less than a week, and I’ll have an appointment with Dr. O. in Chapel Hill after I get back from Boston.

Yesterday was kind of a fun day. I got a Toyota Sienna. It’s a nice van. I got the van so I could take my dog places with me. She was never able to get herself into the back seat of my car. I always had to lift her. I don’t lift anything over 25 lbs anymore, so no more car rides. She doesn’t have trouble stepping up into a van though, so this problem is solved. I hope to take lots of trips over the next few years. I went many years without taking any vacations, and am going to catch up now.

I have an appointment for acupuncture later today. I kind of lost interest in a lot of things over the last 3-4 weeks. I need to get back to doing some of the things that helped me so much in the beginning, like acupuncture and guided visual imagery.

Boston

Jon Siegel is going to be having his stem cell transplant at the Brigham & Women’s Hospital when I’m in Boston, which is right next to the Dana-Farber Cancer Institute, so I’m going to see if I can stop by to say hello. He said he could have visitors, which is nice!

Dex misery

Monday was my dex day (down to 40mg once a week now). I was able to fall alseep at midnight, which was great! But I was awake at 3 am. This may have been due to two factors. Dex causes sleeplessnes and it also causes (in me) really severe indigestion. It’s known to cause ulcers in long term use. My friends are Xanax, Mylanta and OTC Zantac. Sometimes Alka-Seltzer helps, but I have to limit my use of aspirin products since I take some every day for blood thinning.

Dr. Orlowski

Here’s some information about Dr. Orlowski at UNC:

Robert Z. Orlowski, MD, PhD
Assistant Professor, Department of Medicine, Division of Hematology and Oncology
Molecular Therapeutics Program; Clinical Research Program

Clinical Interests
Dr. Orlowski’s clinical areas of focus include the treatment of patients with hematologic malignancies, including multiple myeloma, acute and chronic leukemias, and Hodgkin’s and non-Hodgkin’s lymphomas, and also Phase I clinical trials, which apply novel agents or drug
combinations to the therapy of patients with refractory malignancies.

Research Interests
The research being pursued by members of our laboratory focuses on three goals:

1.) To evaluate the mechanisms by which inhibitors of the multicatalytic proteinase complex (proteasome) induce apoptosis, with a focus on human malignancies in which the oncogene c-myc is involved, such as Burkitt’s lymphoma and breast cancer. Work performed in our laboratory has revealed that proteasome inhibitor-mediated programmed cell death occurs in part through effects on the p44/42 mitogen-activated protein kinase pathway. Current and future studies will evaluate other signal transduction pathways involved in this process, including the c-Jun-N-terminal kinase (JNK).

2.) To determine the potential therapeutic benefit of modulation of proteasome activity for patients with refractory malignancies. Our previous work in this field has included a Phase I clinical trial of the proteasome inhibitor PS-341 in patients with hematologic malignancies, which was the first study to show the activity of this agent in patients with multiple myeloma. Based on an understanding of the mechanisms of action of other chemotherapeutic drugs on cell death and survival associated pathways, novel drug regimens will be evaluated for their anti-tumor efficacy, and those which prove promising will be translated into clinical trials. This approach is exemplified by a current trial of the combination of PS-341 with pegylated liposomal doxorubicin (Doxil).

3.) To examine the potential impact of dietary agents which influence apoptosis-associated signal transduction pathways on the efficacy of cancer chemotherapy. This line of investigation led to our previous demonstration that the dietary additive curcumin can inhibit chemotherapy-mediated apoptosis, generation of reactive oxygen species, activation of JNK, and mitochondrial release of cytochrome c in both in vitro and in vivo models of human breast cancer. Future studies will evaluate the possibility that other factors may also inhibit, or in some cases promote, the anti-tumor efficacy of chemotherapeutic drugs.

Training
Yale University Ph.D. 1990 Molecular Biophysics and Biochemistry
Yale University Ph.D. 1990 Medicine

Board Certifications
Internal Medicine 1994
Oncology 1997

Publications
Small, G.W., Chou, T.-Y., Dang, C.V., and Orlowski, R.Z. Evidence for involvement of calpain in c˝Myc proteolysis in vivo. Arch. Biochem. Biophys. 400: 151-161, 2002.

Somasundaram, S., Edmund, N.A., Moore, D.T., Small, G.W., Shi, Y.-Y., and Orlowski, R.Z. Dietary curcumin inhibits chemotherapy˝induced apoptosis in models of human breast cancer. Cancer Res. 62: -, 2002. In press.

Orlowski, R.Z., Small, G.W., and Shi, Y.Y. Evidence that inhibition of p44/42 mitogen activated protein kinase signaling is a factor in proteasome inhibitor-mediated apoptosis. J. Biol. Chem. In press.