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.

Caution

I just wanted to post a reminder to always check your medications prior to administration. It’s not impossible for mistakes to be made. Thanks to MM list members, I have made it a habit to check everything. Recently I had an Aredia infusion that was ordered to be given over 4 hours. The hospital pharmacy typed 3 hours on the label. I told the nurse, and she went and checked the order. Sure enough, a mistake had been made and she adjusted the flow accordingly.

Something that’s really nice to have is ePocrates on your PDA. I was able to check drug interaction precautions between Thalomid and Zometa vs Aredia. None listed for Aredia, but there’s a warning for Zometa, as we know.

Lesions

I have all my xray/MRI/CT scan films in my possession to take along with me to my appointments with various doctors. Today I pulled out some xrays done in March in Pinehurst to see what I could see. I was just curious. I have a great deal of pain in the right sacral area, and I wanted to look at that. What caught my eye was a film of the right humerus. There were red circles around 2 dark spots on the bone. I compared them to text book images, and they sure do look like small lesions. I’ll consult with Dr. Richardson about these when I see him in less than 2 weeks in Boston at the Dana-Farber Cancer Institute. In any case, I was not told about the possibility that I may have some lesions. This is one reason I am changing local oncologists. I have to beg for information! When I asked the Dr. about the xrays back in March, he said something like, “I don’t remember seeing anything unusual.” I should have asked to him to go check for sure, but just accepted that as an all clear. I really can’t assume anything. Every test has to be followed up on! I’ll be getting a copy of my file to take with me to DFCI in Boston and to Dr. Orlowski at UNC, so I’ll get to see everything that’s been withheld from me so far.

AFLAC

If you’re reading this and don’t have cancer, I recommend the AFLAC cancer policy. I don’t know what possessed me to get this for myself, but I’m glad I did. AFLAC pays money to help cover costs by sending checks for chemo and trips you might make to get a second opinion. So far, they have covered my bone marrow biopsy, each month of Zometa/Aredia, Thalomid and dex. It doesn’t pay for everything, but is intended to provide supplemental coverage. It’s paid directly to you, not the healthcare provider. For example, each month I have received a check for $300 for my Thalomid rxes. I have also received $300 for each of my Zometa infusions. Whatever I paid in was well worth it. I hope I don’t ever need it, but I also bought the long term care policy (AKA nursing home insurance).

My AFLAC rep’s sister has MM.

AFLAC’s web site

Water tested

I sent my water off to a national testing lab for a complete analysis (bacterial, mineral, etc). The results came back, and the only abnormality detected was low pH. I’ll be getting a water treatment system to resolve that. I’ll also get a countertop distiller to use for cooking and washing vegetables. I drink bottled water, but may use the distilled water for drinking too. It’ll save some money on water delivery.

Waterwise Distillation Products

Buying time

All along I’ve thought that I need to hang in here for a few years until researchers find a way to manage MM as a chronic disease or there’s a cure. Bob Meyer just posted something on the MM list that is encouraging. There are many of us who have the same optimism and are doing what we can to keep our disease under control with as little damage to ourselves as possible. Bob’s email to the list follows.

—– Original Message —–
From: “Robert H Meyer”
To:
Sent: Saturday, May 24, 2003 9:21 PM
Subject: [MM] A note of serious hope

Hi All,

Having, like so many of us, taken on the very depressing task of mentally
acknowledging the passing of “Aussie Pat” and Violet Kimball’s husband,
Stanley, and then having sent painful and upset emails to both Chris and
Violet, I decided it was well past time to once again prowl about the
internet to see how things are progressing on MM research.

What I found is extremely hopeful and actually goes well beyond what I had
expected to find. Much of the primary mechanism that “makes MM go” has been
unraveled and moves are well underway to develop methods to disrupt the
vicious cycle of MM cell growth and bone resorption that characterizes most
MM. I won’t go into technical details at this point as I want to keep this
post short and to the point. In any event I have posted some of them
several years ago when they were first suspected. The main thing is that
much has been verified and fleshed out in the last three years so now there
is near certainty about much of the way MM escapes natural controls.

If anyone cares about the technical details, I will post a review (hopefully
in nearly plain English) of what is now known and what is being done. If
anyone wants to see the abstracts for themselves, one good way is to use the
PubMed search engine with the key search directives “OPG AND myeloma” and
“RANK-Fc AND myeloma”. What you will find is extremely uplifting (assuming
you can digest the highly technical terminology).

My main message is that what I am getting from the abstracts is the very
definite impression that some of those on this list who can manage to beat
back their MM for just another few years may quite possibly (I want to say
“likely” but am trying hard to be cautious) outlive their disease. Yes,
there can always be some unexpectedly nasty side effects to the treatment
ideas now being pursued and that could of course lead to disappointments and
some delays as treatment details are further refined – but barring all that
I think the medical community is extremely close to being able to halt the
MM growth cycle in most cases. They don’t yet know what triggers MM, I
think, but they do know an awful lot about how it maintains itself once it
gets started.

Just my personal opinion of what I’m reading in the research abstracts, of
course. I try hard not to be a prophet of false hope but I really am very
impressed at what the medical researchers have managed to figure out about
MM and the way the body loses control over MM cell growth. I certainly
believe that we will very shortly be seeing another new generation of very
promising anti-MM drugs entering the clinical trial gates.

Best wishes all,

Bob Meyer in San Diego county
NO formal medical training but former caregiver to wife (Patricia) dx’d rare
extremely aggressive IgG kappa MM with plasmablastomas and M-spike of 1100
in 4/98, died 11/98 at age 52; prev. MS history; also hepatitis, severe mono

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ePocrates for PDA

If you have a Palm Pilot, you can download a free version of ePocrates, which can be quite handy. It’s like a mini PDR, containing all the pertinent information about drugs. You can select all the drugs you’re taking, and it will display the drug interaction precautions as well. Another nice feature is the insurance formularies. When installing, you select your insurance company, and you’ll be able to tell if the drug is covered by them.