Category: General

In May, I sent out 40 letters to friends, family and business acquaintances in an effort to raise some money for the IMF. Aside from family members, only 4 people sent in contributions. Those are some special people, and I am sending each one a thank you card. The fund drive continues until August 10th. I hope more will respond. Would it not be difficult to help someone you actually know? I’m trying to figure out why some people don’t contribute. If you want to help, send me your name and address, and I’ll get a letter and envelope off to you immediately! Maybe the letter wasn’t appealing enough. Here’s the letter I used (written by the IMF)

Dear ?First_Name?:
Over the years, we have all contributed to many good causes. Now I have a more personal cause. Along with 15,000 other Americans per year who are diagnosed with multiple myeloma, a cancer of the bone marrow, I need your help. The cause of the disease is unknown and there is no known cure. We need more research to find a cure and to develop better treatments for this disease.

There is hope. As a member of the International Myeloma Foundation (IMF), a non-profit organization founded in 1990, I have benefited from a variety of IMF education, research and advocacy programs. I am impressed with the courage of the patients I?ve met, as well as with the volunteers and the small staff that run the IMF. This organization has enabled me to take control and keeps me informed about what I can do regarding the treatment and management of my disease. I?ve also learned that to find a cure, we have to take control of funding more myeloma research. A donation from you will make a difference.

I am asking you to participate with me in Myeloma Awareness Week?s fundraising campaign. People from all over the U.S. are sending out letters like this to everyone they know. Please make your donation to the International Myeloma Foundation before August 10th, 2003. An envelope is enclosed for your convenience. The grand total of the funds raised will be announced during Myeloma Awareness Week. Thank your for your friendship and support.

Does anyone have any suggestions?

I was recently looking through a vitamin catalog, and found an item called MGN-3. MGN-3 enzymatically integrates rice bran with medicinal mushroom extract via hydrolysis. The claim is that it triples natural killer (NK) cell protection, enhances B-cell & T-cell activity and increases interferon levels.

–> Lane Labs, manufacturer of MGN-3

     One multiple myeloma patient was a 58-year-old man diagnosed in 1990. 
     He under- went several months of chemotherapy following his diagnosis. 
     Although his condition seemed to stabilize, his blood still showed markers 
     for multiple myeloma eight months after chemotherapy. 



     He then began taking MGN-3 and in less than 6 months, follow-up lab work 
     showed no indication of cancer. Today eight years after his initial 
     diagnosis, he is the first patient known to have survived multiple myeloma, 
     according to Dr. Ghoneum. 
     
     From http://research-data.com/Latest-Findings/MGN-3-Natural-Pharmacy.htm

     (Dr. Ghoneum is the developer of MGN-3)

The FDA is taking action against Lane Labs, a manufacturer of MGN-3:
–> The story from Natural Products Industry Insider

–> Quackwatch article from 2001

Is MGN-3 waste of money or could it possibly be helpful? I did a search on the ACOR listserv for MM, and came up with a few real life stories. Rather than quote them here, you can do your own search and read for yourself.

Based on what I’ve read, it’s not known to have any harmful side effects and doesn’t appear to intefere with treatment. You would have to make up your own mind about whether or not to give it a try, after having consulted with your oncologist. I’d be interested in hearing from anyone who has been using it.

My nephew is going to be attending a school in Greensboro, NC next year. It’s not too far from here, so we may get to see him more often! AHA

This is where I went to school for most of high school. Why I left is a long story, having to do with misbehavior. It was a long time ago!

From Bob, on the ACOR MM list:

Date: 2003-06-30

New Study Demonstrates Bone Protein Can Reverse Kidney Failure

BOSTON – A new study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) has shown that a protein used to heal fractured bones is effective in repairing and reversing chronic renal disease, a leading cause of morbidity and mortality throughout the U.S.

These findings, which are reported in the July 2003 issue of Nature Medicine, could help lead to the development of a therapeutic alternative for the nearly 300,000 kidney disease patients who are currently undergoing dialysis.

“Dialysis is not really a treatment, it’s just a means of survival until an opportunity for a transplant opens up,” notes the study’s senior author Raghu Kalluri, Ph.D., director of the Center for Matrix Biology at BIDMC and Associate Professor of Medicine at Harvard Medical School. “This is a very tedious way of living life,” he adds, explaining that the process of
mechanically filtering blood through a machine to remove waste products must be performed several times a week for a period of three to four hours per visit, posing risks of infection and other side effects. Furthermore, the procedure is extremely costly.

The kidneys function as a filtration system, keeping the body’s blood supply healthy by removing excess fluids and wastes, as well as by producing hormones. When kidneys “fail” – as can result from complications associated with diabetes, lupus or several other diseases – harmful wastes accumulate in the bloodstream, excess fluids build up in the body, and red blood cell production is impeded. Once chronic kidney disease develops, it cannot be reversed or repaired; when the organs cease to function, patients have no alternative but to undergo dialysis while awaiting a kidney transplant.

This new study looked at the role of a molecule called bone morphogenic protein (BMP)- 7 which, in its recombinant form, has been approved by the U.S. Food and Drug Administration for the treatment of bone fractures. Earlier studies had revealed that BMP-7 is highly expressed in the kidneys of healthy individuals. “We wanted to learn if this protein was somehow offering protection against kidney injury,” explains Kalluri.

The investigators used mouse models of chronic renal injury, characterized by the presence of scar tissue known as renal fibrosis; once kidney disease was well-established in the animals, they administered human recombinant BMP-7.

“We found that in the kidneys, BMP-7 reverses a process known as epithelial-to-mesenchymal transition, which generates scar-causing cells known as fibroblasts,” says Kalluri, explaining that BMP-7 first reduces the number of the fibroblast cells, and then replaces the damaged areas of the kidney tubules with healthy epithelial cells. “In effect,” he adds, “BMP-7 is decreasing the bad cells [in this context, fibroblasts] and converting them into good cells [in this context, epithelial cells].”

Although therapies exist to slow progression of kidney disease, once it has developed it becomes intractable, eventually leaving patients no alternative but to undergo dialysis. “The possibility of creating a cost-effective drug that would actually reverse renal injury could significantly reduce the need for dialysis and significantly improve the quality of life for these
patients,” says Kalluri.

### Study co-authors include BIDMC investigators Michael Zeisberg, M.D., Jun-ichi Hanai, M.D., Hikaru Sugimoto, M.D., Ph.D., Tadanori Mammoto, Ph.D., David Charytan, M.D., and Frank Strutz, M.D.

This study was funded by grants from the National Institutes of Health, Deutsche Forschungsgemeinschaft, and support from the Center for Matrix Biology, BIDMC. Ortho Biotech Products, L.P., is the exclusive licensee of BMP-7.

Beth Israel Deaconess Medical Center is a major patient care, teaching and research affiliate of Harvard Medical School, and ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a founding member of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox.

Editor’s Note: The original news release can be found here:
http://home.caregroup.org/newsnow/pr_out.asp?pr_id=431

I’m getting closer to my doctor’s desired INR for me. I’m now at 1.99, and he would like to see me between 2 and 3 (but closer to 2). I’ll stay on 10 mg of coumadin a day for now, to see if that gets me to 2.

We had a tornado in the area today. I didn’t know about it until I arrived at the clinic and saw that the lobby was virtually empty. They cleared people out as a precaution. It turns out the tornado was just passing by. It didn’t touch down.

I’ve noticed that when I take my weekly dex, the next day or so I have a really red face. It looks like I have sunburn! My skin even peels a bit. Usually by the end of the day on Wednesday I’ve recovered.

I have to have my INR checked today for coumadin. Let’s hope I don’t have to increase my dose anymore. I just hate having to take more pills.

If you’re reading this and you’re a smoker, please quit!

I signed up for two classes to continue with my graduate studies. I had taken off spring and summer semesters There was a lot to do and think about right after diagnosis, and I wanted to avoid the added stress of tests and paper deadlines. Also, my first dex pulses were 4 days on and 4 days off, and I was exhausted that entire time. I don’t think I could have done anything! If I miss more than 2 semesters, I have to reapply! What a pain that would be. So I went ahead and registered for classes for fall semester. After I finish fall semester, I’ll be half way through the program. I hope to have my master of science degree done in the following two semesters.

I just took Ambien. I don’t want to be up until the sun comes up. :)

This is an abstract brought to our attention by K.B. on the MM listserv.

Published online July 15, 2003

Blood, 15 July 2003, Vol. 102, No. 2, pp. 417-418

Angiopoietin expression in multiple myeloma

Multiple myeloma demonstrates a progressive, and usually fatal,course, with current treatments generally producing only temporary remissions. Antiangiogenic therapies represent a potential new approach to treating this cancer. While it is well established that growth in solid tumors is dependent on angiogenesis, the role of this process in hematopoietic tumors is not fully appreciated. There is a strong correlation between increased angiogenesis and poor survival in myeloma patients. Furthermore, both cellular and circulating levels of vascular endothelial growth factor (VEGF) are often elevated in hematologic malignancies, including myeloma, and have been shown to predict for a poor outcome, lending additional support to the concept that angiogenic cytokines are involved in the growth and progression of these malignancies.
In this issue, Giuliani and colleagues (page 638) extend our knowledge of marrow angiogenesis with their report on the expression of angiopoietin-1 in myeloma cell lines and patient samples.
Angiopoietin-1 (Ang-1) was found to be expressed in 47% of the patient samples examined. Bone marrow angiogenesis was examined and found to be elevated in 12 of 15 patients examined (80%), and there was a significant correlation between Ang-1 expression and microvascular density (MVD), although no such correlation was present between Ang-1 and Tie2 expression. Giuliani and colleagues were also able to demonstrate that myeloma cells could up-regulate the angiopoietin receptor Tie2 in human bone marrow endothelial cells. Conditioned medium from myeloma cell lines was capable of stimulating angiogenesis, although such stimulation did not occur in the presence of an anti-Tie2 antibody. Angiopoietins, while not believed to be involved in the initial stages of angiogenesis, are known to play an essential role. Ang-1, acting through Tie2, contributes to the stabilization of newly formed vessels via recruitment of peri-endothelial supporting cells as well as endothelial cells, whereas Ang-2, also acting through Tie2, reduces these interactions, leading to vascular regression. It has also been reported that coexpression of Ang-2 and VEGF promotes new vessel sprouting and has been shown to predict a poor prognosis in myeloma and other malignancies.

The role, if any, of angiopoietins in myeloma is far from clear, however. Uneda et al have also recently reported their findings regarding angiopoietin expression in myeloma (Haematologica.
2003;88:113-115). In their study, 27 of 36 multiple myeloma patients studied showed expression of Ang-2 by reverse transcriptase?polymerase chain reaction (RT-PCR) and immunohistochemistry. Coexpression of VEGF and Ang-2 was detected in 18 of the myeloma samples. The survival rate was significantly lower in those patients expressing Ang-2. Interestingly, and in contrast to the findings by Giuliani et al, they found no evidence of Ang-1 expression.

The seemingly contradictory findings of Ang-1 and Ang-2 expression in these 2 studies should be carefully interpreted in the context of how the cells were isolated and examined. Both studies examined relatively few patients, and in neither study was the effect of the bone marrow microenvironment on expression of these molecules fully taken into account.

Several important outstanding questions remain to be addressed. First, the apparent contradiction in the results from these 2 studies must be resolved. Does expression of Ang-1 or Ang-2 have prognostic value in myeloma? The results from Uneda et al would suggest so. Does angiopoietin expression vary with the stage of the disease? Do the angiopoietins represent valid therapeutic targets? Even if the angiopoietins are not the major driving factors in marrow angiogenesis, the results of Giuliani et al suggest that they may represent a valid target. Although it is too early to answer these questions, the preliminary evidence is tantalizing.

William T. Bellamy
University of Arizona

Related Articles in Blood Online :

Proangiogenic properties of human myeloma cells: production of
angiopoietin-1 and its potential relationship to myeloma-induced
angiogenesis.
Nicola Giuliani, Simona Colla, Mirca Lazzaretti, Roberto Sala,
Giovanni Roti, Cristina Mancini, Sabrina Bonomini, Paolo Lunghi, Magda
Hojden, Giovenzio Genestreti, Mirija Svaldi, Paolo Coser, Pier Paolo
Fattori, Gabriella Sammarelli, Gian Carlo Gazzola, Regis Bataille,
Camillo Almici, Cecilia Caramatti, Lina Mangoni, and Vittorio Rizzoli
Blood 2003 102: 638-645.