Rattling the clone’s cage…

Yesterday I discussed my results with Sherlock who expressed caution based on the fact that I had changed hospital labs (see yesterday’s post). Now, I am all in favour of being cautious. However, last night Stefano reminded me that Sherlock (who btw hasn’t been testing anything new but has been taking only curcumin and fish oil) went to the same hospital for her most recent tests, and her results were stationary compared to her previous Careggi tests. Those are good results, of course!

But let’s go over Stefano’s considerations:

1. Sherlock’s test results haven’t changed since last spring.

2. Mine have.

3. Our results were processed by the same hospital lab, i.e. the new one (“new” to us, of course!), less than a week apart.

4. Therefore, the huge drop in my total IgG as well as a not-so-dramatic-but-still-relevant drop in m-spike seem to indicate that something has definitely changed in my case.

5. Whether or not the changes in my numbers can be ascribed to ashwagandha is impossible to say. But the evidence does seem to point in that direction.

One thing is crystal clear: I will have to re-test ashwagandha again, probably after my saw palmetto experiment. Sherlock suggested that I drop the saw palmetto and test ashwagandha now, but I think I will wait…mainly because of the menstruation reoccurrence (see my October 5th post). I didn’t care for that one bit. I would like to see if I still continue to get my period, now that I have stopped taking ashwagandha.

On to a related subject. Since I published my post, in addition to the public comments left on my blog, many of you have written private congratulatory notes to me (thank you, everyone!). One of these notes came from a long-time blog reader and MGUS friend, who began taking ashwagandha last week. Her writing is always witty and engaging, as we can tell by the end of her message, which really tickled my funny bone:

“Your latest results have made me feel really good about my choice to use ashwagandha to rattle the cage of my clone.”

Rattling the cage of the clone…I love this image! Well, let’s keep rattling away…without making “the clone” too angry, though!!!


What I am about to write may sound almost too amazing to be true, and perhaps it is. When I got home from work today, I found my early October blood test results lying in my mailbox. Surpriiiiise!!! According to the schedule, you see, my results weren’t supposed to be mailed off until October 21st!!! My knees began shaking so much that I almost didn’t make it to the front door (oh well, okay, that’s actually not true; I just thought it would be neat to introduce some drama…teehee).

Well, I confess, I am ecstatic…even though, as prudent Sherlock reminded me, these results must be examined with a certain degree of caution because they were not processed at Careggi university hospital but at another one of Florence’s main hospitals (my reason for switching hospital labs can be found in my October 5th post, btw). A very good hospital, mind you. But that also means that a lot of my numbers now have different reference ranges. In some cases, though, thank goodness, the old and new ranges were identical, which made my job much easier. Okay, that said, here are a few values:

The following gives me a good reason to celebrate: my total IgG has gone down from a whopping 39,9 (June 2009 tests) to 29,7 g/L. No kidding. A more than 30 % drop! Incidentally, the reference range happens to be the same for both hospitals, except one is in g/L, the other in mg/dL, which simply means that I went from 3990 to 2970 (mg/dL, i.e.).

Trallallero trallallà!!!…brief dance of joy.

Now, my M-spike (or rather, what Sherlock and I believe to be the number corresponding to the M-spike, though this will have to be confirmed by our respective hematologists) has gone down from 2,68 to 2,41. That would also be a very good result: a drop of more than 10 %.

As for the rest of my results, taking into account the above-mentioned range differences, it would seem that…

1. my platelet count has increased to 305 (new range: 150-400) from June’s 244 (Careggi range: 140-440).

2. my serum calcium and creatinine are stable…still within the normal range. And my IgA and IgM also remain unchanged. Phew!

3. my C-reactive protein, which till now has been a maddeningly “less than” amount, is finally an ACTUAL NUMBER: 0,3 mg/L (normal range: <0,5). Good to know.

4. my monoclonal component has gone down from 28,3 % to 25,7 %. Another slide in the right direction!

5. my total protein seems to be stable, still slightly above the normal range, but, due to the difference in ranges, I will have to do a few calculations later on, with Stefano’s help. It looks about the same to me, though.

6. I am almost positive that my hemoglobin and hematocrit have increased. Hard to tell because of the, yes I am sure you have guessed!, slight range difference. My hematocrit has certainly gone up…Oh, and so has my white cell count.

There are a few bad things (can’t have everything, after all):

— my B2M appears to have gone up a bit. But yes, as you may have guessed (again!), the new reference range is lower than the Careggi one. Even so, my B2M is only slightly above the normal range. I am not concerned.

—  my vitamin D has decreased compared to June, in spite of my vitamin D supplementation over the summer, so I will have to do something quickly about that…this is a matter of some concern to me, now that the flu season has definitely struck Florence. This number is still within the normal range, but it is located on the lower end, which I know is not good at all!

Well, I am definitely in the mood to make merry this evening, as is Stefano, who slyly asked me over the phone if I wanted to celebrate this happy occasion with tripe and onions for dinner…yeah, right!!! He knows that I would rather eat my own shoelaces! Silly boy… 🙂

Saw palmetto and multiple myeloma: the full study

A blog reader, an 8-year survivor of multiple myeloma, recently told me that he began taking curcumin last summer, after reading my post on the curcumin-bortezomib study. This combination, he believes, produced much better results than the Velcade alone would have. Based on my July 23rd 2009 post on saw palmetto, or Serenoa repens, he began taking that as well. He isn’t sure that it helped, but he writes that his m-spike, which had seemed stuck at 0.3, subsequently went down to 0.1. Interesting.

Well, that reminded me that I hadn’t yet posted about the full saw palmetto study (abstract: http://tinyurl.com/mxrysb), which I purchased online a few days ago, since saw palmetto happens to be next in line on my to-be-tested list of supplements…all depends on the content of this study. So let’s stick our heads right into the full study.

After the usual well-known dire statistics about myeloma (skipskipskippety!), the study mentions STATs. These signal transducers have an important role in myeloma (which reminds me, I have an almost-finished draft on STAT 3…need to find the time to finish it, sigh). Just to mention one of its actions, STAT 3 stimulates the growth of our malignant cells. Oh, and another thing: it protects them from apoptosis.

Then we find a list of previous studies on the effects of saw palmetto on prostate cancer and breast cancer. By the way, I am going to use “saw palmetto” and not “Serenoa repens” in this post, since I rather like the image of a “saw” being “palmettoed” through each myeloma cell…and no, “to palmetto” is not a reeeal verb…just an invented image of my twisted brain, hehe…

In this study, the researchers found that Serenoa repens inhibited the proliferation of a variety of human leukemia cells including U266 and RPMI 8226 multiple myeloma cells. We also found that Serenoa repens inhibited basal level of phosphorylated form of STAT 3 and Interleukin-6 (IL-6) induced level of phosphorylated form of STAT 3 in U266 cells suggesting that Serenoa repens may induce growth arrest and apoptosis of human multiple myeloma cells through inactivation of STAT 3 signaling. Serenoa repens might be useful for treatment of individuals with human multiple myeloma. By the way, the cells lines used in the study were human acute myelogenous leukemia and acute lymphoblastic T-cell cells (HL-60, NB4 and Jurket) and multiple myeloma cells (U266 and RPMI 8226).

Results: in addition to stopping the growth of the myeloma cells, saw palmetto also slaughtered them without pity, in a dose and time-dependent manner. Interesting finding: U266 cells exposed to saw palmetto had 60% lower levels of Mcl-1 compared to control cells (Mcl-1 is an evil member of the Bcl family; in a nutshell, it helps myeloma cells survive). Let’s see, without boring you with too many details, here is the gist (my emphasis): These results indicate that Serenoa repens induces growth arrest and apoptosis of human MM Cells. Yaaaay!

The researchers also showed that saw palmetto inhibits the proliferation and determines the death of human acute leukemia cells. Also very good.

And they discovered that saw palmetto reduces the expression of phosphorylated form of STAT 3 by 80 %. Not bad, not bad at all. It also blocked the IL-6-induced phosphorylation of STAT 3 by 85.0%. This leads the researchers to state the following: These data indicate that Serenoa repens may reduce the expression of phosphorylation of STAT 3 or ERK mediated by IL-6 in MM cells. Well, even if you don’t understand every single detail of the above, no matter: all we need to know is that the above-mentioned reduction is a very very GOOD thing.

The researchers also examined the interaction of saw palmetto with a chemo drug used in the treatment of myeloma and other types of cancer: docetaxel. I was not surprised to read that the anti-myeloma activity of this drug was enhanced by saw palmetto through inhibition of STAT 3 signaling.

Discussion: In this study, we found for the first time that Serenoa repens down-regulated the phosphorylated form of STAT 3 in U266 cells. Also, IL-6-induced the level of phosphorylated form of STAT 3 and ERK were reduced after Serenoa repens treatment in U266 cells. Again, it doesn’t matter if we don’t understand what the process of phosphorylation entails. The point is: this is very good news for us.

This leads us straight to the researchers’ final statement: In summary, we found that Serenoa repens was an important phytotherapeutic drug against multiple myeloma cells through inhibition of STAT 3 signaling. Serenoa repens may be useful as an adjunctive therapeutic agent for treatment of individuals with multiple myeloma and other types of cancer in which STAT 3 signaling is activated.

Okay, I am convinced. I am going to begin taking saw palmetto today. Just to be cautious, though, I will take it at a different time of day than my curcumin/fish oil. Let the experiment begin! Oh, I see it’s time to feed my cats…I had been wondering why they were walking across the desk, waving their tails in my face…I had better stop here. Ciao!

Upcoming seminar for multiple myeloma patients/families/caregivers in Florence

A seminar for myeloma patients and their families/caregivers will be held here in Florence on Wednesday, October 21st, at the 15th century Villa La Pietra, now owned by NYU. I received this bit of news just this morning. I plan to attend, of course, since (luckily!) I don’t work on the 21st. This will be my first myeloma patient seminar. Ever. I can’t wait. The main speaker, by the way, will be Dr. Brian Durie. Important: you have to sign up in order to attend (for free, eh). See details below.

If any of you plan to be there, please please please get in touch with me via the Contact form (or, if you have my e-mail address, drop me a line). I would love to meet you!

Here follows the info that I received from the seminar organizer, Vittorio Schirinzi:

Come promesso, sono a darvi il programma del prossimo 21 ottobre per il II Seminario Pazienti e Famiglie che questo anno si terrà a Firenze. Sede del Seminario è Villa “La Pietra” sita sulla Via Bolognese al civico 120.

Come lo scorso anno, parteciperà al Seminario il Dr. Brian Durie che alcuni di voi hanno avuto il piacere di conoscere. Il Dr. Durie è uno dei massimi esperti mondiali sul mieloma multiplo e sarà disponibile a rispondere a tutti i quesiti che vorrete sottoporre. La presentazione del Dr. Durie e le domande e risposte saranno interamente tradotte da un interprete professionista per coloro che non parlano inglese ed al fine di facilitare al massimo la comprensione.

Vi invito a partecipare a questo evento poiché è la migliore occasione per poter risolvere alcuni vostri dubbi e avere delle risposte concrete ai vostri quesiti sul mieloma multiplo. Vi ricordo che la partecipazione è totalmente gratuita confermando la vostra presenza via e-mail all’indirizzo mielomahelp@gmail.com  


 Programma Seminario Pazienti Mieloma Multiplo. Villa “La Pietra”, Firenze 21 ottobre 2009.

Ore 15:00 Apertura Seminario

Susie Novis, Presidente International Myeloma Foundation e Vittorio Schirinzi Presidente Associazione Schirinzi A. Mario

Ore 15:15 “Che cosa è il mieloma multiplo”

Dr. Brian Durie, Cedars Sinai Hospital, Los Angeles

Ore 15:45 “Attività Mieloma Multiplo nell’Area Fiorentina e Novità nella terapia del Mieloma Multiplo”

Dott.ssa Chiara Nozzoli, Reparto di Ematologia Ospedale Careggi, Firenze

Ore 16:15 La parola ai pazienti: domande ai relatori 1° parte

16:45 Coffee Break

Ore 17:15 La parola ai pazienti: domande ai relatori 2° parte

Ore 18:00 Chiusura seminario

Greg Brozeit, International Myeloma Foundation e Vittorio Schirinzi, Associazione Schirinzi A. Mario


Se avete intenzione/la possibilità di partecipare a questo seminario, vi mettereste in contatto con me? Se non avete il mio indirizzo e-mail, mi potreste lasciare un commento su questo post oppure cliccare su “Contact” (qua a destra, sotto “Pages”). Mi farebbe molto, ma davvero molto!, piacere incontrarvi! A proposito, per ulteriori informazioni (tipo, come arrivare a Villa La Pietra oppure la biografia del Dr. Durie), date un’occhiata al sito di Mieloma Help: http://mielomahelp.blogspot.com/ Ci vediamo a Villa La Pietra, spero!

Peekaboo in a bag…

I am reading, or trying to read!, the full dendritic cell study (see my October 6th post) and also recovering from some sort of minor “bug,” that held me captive for about 24 hours this week. No big deal, I am fully recovered now…in fact, I went back to work today and feel 100% fine…but I am being cautious. I found out just this morning, you see, that one of my students, who has been absent from work for two weeks with the flu (nobody knew if it was the H1N1 virus), has now come down with bronchial pneumonia, poor sweetie. As a consequence, antibacterial hand sanitizer pumps have been put in all the company bathrooms…something that has never been done before. Wise move, I say!

This is a photo that I took last night of PeekabooIMG_3351, our youngest kitty, playing inside a paper shopping bag on my parents’ bed. You will notice that the bag’s handles have been cut. There is a good reason for that.

Once, as a kitten, our male cat, Piccolo, got his head stuck inside the handle of a plastic shopping bag…and he (understandably!) completely freaked out. He began flying up and down the stairs with the bag dragging after him (he could easily have choked!), with both of us scampering madly after him, trying to set him free, which Stefano managed to do in the end. Luckily, apart from his getting a huge fright (he peed all over the stairs, poor dear) AND giving Stefano and me the fright of our lives, no real harm was done. But we learned a valuable lesson: if you let your pet play with a bag, always make sure that the handles are cut. And never, under any circumstances, leave a bag of any sort lying around the house.

Well, I am going to stick my head inside that dendritic cell study again…I must have been a huge masochist in a previous life…yes indeedie!

P.S. My blog banner photo was taken by Stefano at the Oasi di Focognano, a WWF oasis located right outside Florence, where we went last weekend to photograph migrating birds. In addition to dozens of great and small white egrets and grey herons (like the one in the banner), we saw a stork, too. Fabulous!

Corrupt immune system cells

A myeloma list friend (thanks!) posted about a Science Daily article discussing a recent discovery that may be of fundamental importance for future myeloma research. See: http://tinyurl.com/ye6d5bu

Bad news: our immune system cells (=plasmacytoid dendritic cells, specifically) can be tricked into protecting the blasted myeloma cells, thus promoting their growth and general wellbeing…

Good news: this process may be reversible.

Well, well, interesting…go have a look…

Astonishing ashwagandha…

Stefano and I went to have our blood tests on Saturday. His were merely part of a routine check-up…mine were the usual myeloma ones, with a few extra tests thrown in, as you will see.

Through Sherlock (I thanked her privately but this deserves a huge public note of thanks, grazie, carissima!), I discovered that you can call and make an appointment to have your tests done at a hospital that is about a ten-minute drive from our house. If you make an appointment for 8 AM, you are done by 8:10 AM, more or less. Wow. You have no idea how thrilling this is. My life is about to change…no more endless hours spent in the vast waiting halls of Careggi university hospital, which, at this time of year, is very likely packed to the brim with flu-infested coughing and sneezing people. Yaaay! But I digress…

The point of today’s post. For three weeks in September I tested ashwagandha, or Withania somnifera, a medicinal plant used as far back as ancient Egypt (!) and, in more recent years, found to have anti-myeloma activities (see my page on “Ashwagandha” or my June 15 2007 post). I took it separately from curcumin, just to be cautious. And I took the recommended dose on the bottle. No more, no less.

So these were my ashwagandha tests. I really hope that even the low dose I took had a positive effect on my MM markers. Fingers tightly crossed!

But I wanted to mention a couple of rather odd things that happened during the ashwagandha period…not necessarily bad things, but certainly out of the ordinary. As follows.

1.  I felt more tired than usual. I mean, REALLY TIRED. Whenever possible (not at work, i.e.!), I would fall into a deep sleep, especially after lunch…and it would take a colossal effort on my part to wake up in mid or late afternoon. This didn’t make any sense. 

Ashwagandha, you see, is supposed to give you energy. It translates into something like “the vitality of a horse.” A horse?! Hah. In my case, the translation should be: “the vitality of a sloth.”

I went online and read somewhere (a forum, I think) that ashwagandha can make some folks tired. Okay, no problem. Mental note: next time (for I am sure I will try ashwagandha again, even if my tests don’t turn out as fabbbbulous as I hope), take it before going to sleep.

2. Now for a more, er…private topic. Not an easy one for prudish little moi. But for the sake of science, I will set aside my modesty for just a second. Here goes.

I stopped having my menstrual period quite a few months ago: in January 2009, to be precise. After ascertaining that I was not pregnant (a relief for many reasons, mainly my condition of having SMM, but also my age, 47 at the time; I am now 48), I simply decided that I had hit menopause. No big deal. You see, I have always belonged to the “hate-my-period-with-a-passion” category of women, so “losing” my period was almost cause for a champagne/chocolate truffle celebration. No, I never experienced unbearably painful menstrual cramps, I never became moody or irritable (as far as I know…), nothing like that…I just have always hated getting my period. Period.

I made an appointment to see a gynaecologist who checked me out thoroughly last spring, including an ultrasound. Tutto bene, she told me (=everything is just dandy). She agreed that I might have entered menopause but didn’t exclude that I might have a period at some indefinite point in the future. She prescribed specific menopause tests, which I had on Saturday, in fact.

Well…about two and a half weeks after beginning ashwagandha, aunt Flo (=euphemism!) popped in to visit me for about a week. An unwelcome visit, to say the least. Uffa!

I remembered reading that ashwagandha was used as some sort of sexual tonic in Ayurvedic medicine. I had a look online, where I found that ashwagandha is still traditionally used to treat loss of libido in men and, tadaaa!, sterility in women. Does that imply that it has the ability to start up a menstrual period again? No idea.

In spite of my uncertainty about the ashwagandha-period link, I decided to publish this post because I found something that might be of interest to those taking doxorubicin, which, at high doses, is known to damage the heart. Tests carried out on rats show that ashwagandha may play a role in the protection against cardiotoxicity and thus might be a useful adjuvant therapy where doxorubicin is the cancer-treating drug, see: http://tinyurl.com/ydw3k7k 

In fact, ashwagandha has some remarkable properties, more than I had realized, to be honest…just go to PubMed (http://www.pubmedcentral.nih.gov/) and type in “ashwagandha” together with whatever you want to look up, e.g. “diabetes” “stress” “anxiety” “Parkinson’s disease” “cystic fibrosis” “arthritis” or “glioblastoma.” Oh, and osteoporosis, see this 2006 study, e.g.: http://tinyurl.com/yc8o946

And finally, here is a link to read an extremely interesting 2006 review of ashwagandha, including references to, and details of!, scientific studies: http://tinyurl.com/yeaggrc (those doing radiotherapy or chemotherapy, e.g. cyclophosphamide and paclitaxel, should have a look at the “Chemotherapy Interactions” section). Good stuff!

Ranting and raving

I am still astounded at what I read yesterday in the October 1 newsletter of one of the main myeloma organizations. At first glance, I thought that the news item about denosumab, a monoclonal antibody currently under study for the treatment of osteoporosis and some types of cancer, including multiple myeloma, sounded quite interesting.

The title: “Amgen has positive results from Phase III trial of denosumab.” And the item reads as follows: Amgen announced results from a Phase III trial of denosumab in advanced cancer patients with multiple myeloma or solid tumors that showed the drug delayed the median time to first on-study skeletal related event by 4.3 months.

I wanted more information, so I clicked on the “read more” link. To my surprise, I was led DIRECTLY to Amgen’s own press release about denosumab. Huh? Hello??? Is a drug company’s press release considered to be an unbiased, reliable source of information? I mean, what if I based my blog research entirely on press releases and/or information from Heather’s Healing Herbs & Potions (=an invented company name, btw)? I think you get my point. Ridikkulus!

Well, I decided dig deeper. Let me make it clear that I had no idea that I would uncover any problems. But I did. Yes indeed, there may be some very serious problems with denosumab. Now, I don’t usually rant and rave, nor do I even like to rant and rave, but I think this deserves a bit of a rant.

It didn’t take me long to find a number of unsettling details concerning denosumab. See, e.g., this MedPage Today article titled “FDA Questions Denosumab Safety in Advisory Meeting Documents,” based on evidence from a denosumab-osteoporosis trial: http://tinyurl.com/ya6h99s

From the FDA report (taken from the above link): “Overall, subjects in the denosumab group had a slightly increased incidence of serious infections,” according to the briefing document. “There were more serious infections of the skin, ear, abdominal system and urinary tract. Also, endocarditis, infected arthritis and skin ulcers occurred more commonly in denosumab subjects. There were three denosumab subjects in phase I studies who developed pneumonia requiring hospitalization following a single dose of denosumab.” The document also noted that while Amgen did not perform carcinogenicity studies in animals because denosumab is not active in normal mice or rats, the clinical data showed a modest increase in certain malignancies in the human subjects. “Three subjects receiving a high dose of denosumab in [a] dose-finding study died of a new malignancy,” the staff review found. Those individuals received 100-mg doses, whereas 60 mg was used in the phase III studies and would likely be the recommended dose upon approval.

(I cannot quote the entire thing, but to read more just click on the above tinyurl link. Make sure you read the part about the “unhealthy changes in bone structure.” Oh, btw, let us not forget that, apart from having osteoporosis!, the trial participants were otherwise healthy women…)

The question is obvious: shouldn’t immunocompromised patients be informed of any potential problems, particularly the possibility of developing “serious infections”? Bloody hell, indeed we should!!! Infections kill so many of us…

But in the myeloma organization’s newsletter, and of course (duuuh!) in the Amgen press release, you will find nothing about all these potentially very serious issues for myeloma patients. Not one word. Hmmm, I just discovered also that Amgen is one of the MM organization’s corporate sponsors…no comment necessary…

To say I am disappointed is to put things mildly. I am bloody outraged! When our own myeloma organizations start using drug company press releases to provide us with important medical information, it is our duty to speak out.

This is rubbish, absolute rubbish.

Things have got to change. We can no longer afford to ignore the heaps of scientific studies that demonstrate the anti-myeloma effects of non toxic plant extracts. These compounds have the potential to improve the quality of our lives without harming us in any way (I am a case in point)…furthermore, many of them have been used for thousands of years in Ayurvedic medicine, that is, they already have a good safety profile.

For those of us who are stable, these compounds may slow down, or perhaps even halt!, progression to active myeloma. And heck, there may even be a cure for myeloma in there somewhere. But we will never know for sure, unless these compounds get tested, alone and in combination, in a clinical trial setting.

It is time for us to demand that the promising, non toxic compounds, such as picropodophyllin, be tested in MM and MGUS and SMM clinical trials. Not some day in the bloody future, but RIGHT NOW!!! 

[More details: http://tinyurl.com/ycap484]

IGF-1, the American mayapple, curcumin and multiple myeloma. Part II

First, I searched PubMed to see if curcumin possibly inhibits this growth hormone that has such a negative impact on myeloma patients. Hah. Quelle surprise! It does! So curcumin-takers are a step ahead, it would seem. Here are the two main studies:

  1. A 2008 study on colon cancer cells, chemo and curcumin (see: http://tinyurl.com/yajdk5s) found that the superior effects of the combination therapy of curcumin and FOLFOX are due to attenuation of EGFRs and IGF-1R signaling pathways. We also suggest that inclusion of curcumin to the conventional chemotherapeutic agent(s)/regimen could be an effective therapeutic strategy for colorectal cancer. (FOLFOX, btw, is a chemo regimen for patients with colorectal cancer.)
  2. A 2007 breast cancer cell (=MCF-7) study showed that curcumin exhibited a potent ability to blunt IGF-1-stimulated MCF-7 cell growth and reverse the IGF-1-induced apoptosis resistance. See: http://tinyurl.com/ye3jqje

I then checked out some of the other anti-myeloma, non toxic substances discussed on my blog. Bingo, again. Here is just a sampling of what I found:

  • 2009 study on resveratrol and genistein: Polyphenol treatments decreased cell proliferation and insulin-like growth factor-1 (IGF-1) protein expression in the prostate, see http://tinyurl.com/yesbb5q
  • 2008 study (see: http://tinyurl.com/yea69yn): resveratrol significantly inhibited IGF-1 in breast cancer cells.
  • The 2008 myeloma-parthenolide study that I posted about on June 4 2008 (see my Page on parthenolide or click here for the full study: http://tinyurl.com/ydousu2) shows that parthenolide, extracted from the feverfew plant, overcame the proliferative effects of cytokines interleukin-6 and insulin-like growth factor I, whereas the adhesion of MM cells to bone marrow stromal cells partially protected MM cells against parthenolide effect. (Blasted adhesion!)
  • 2009, prostate cancer-EGCG study (see: http://tinyurl.com/ydkbgw3). EGCG decreased the levels of IGF-1 (as well as having other beneficial effects). Same thing for colorectal cancer, see http://tinyurl.com/yat8wjt .

This post could easily turn into a long boring laundry list, so I will stop here. However, if you want to find out if any of the supplements that you are taking might inhibit IGF-1, just go to PubMed (general link: http://www.ncbi.nlm.nih.gov/) and type in your key words. Easy peasy.

Let’s move on. I would like now to discuss a Science Daily article that I read in September: http://tinyurl.com/ydxxcgm It gives us an overview of podophyllotoxin, an anticancer compound extracted from the roots and rhizomes of an endangered Indian medicinal plant but also from those of the common American mayapple (for an overview of this plant: http://tinyurl.com/yccs83x). This compound, incidentally, is found in the chemo drug etoposide, used to treat lymphoblastic leukemia, brain tumours and other types of cancer. The abstract of the study discussed in the SD article can be found here: http://tinyurl.com/nh4grx

As usual, I checked PubMed, where I found that picropodophyllin was tested in 2007 against myeloma cells, too. Hah! And, double hah!, the full study is available online: http://tinyurl.com/y8p4nzh The results are astounding: targeting the IGF-1R using picropodophyllin (PPP) in a therapeutical setting not only has strong antitumor activity on the established MM tumor but also influences the BM microenvironment by inhibiting angiogenesis and bone disease, having a profound effect on the survival of the mice. Wowie.

An important point: this study tested the impact of PPP in models of established myeloma, that is, not just on MM cells. They used what is called the 5T2MM mouse model, representing an in vivo model of established, slow growing myeloma. Now, you can read the details on your own (the study isn’t a difficult one compared to others I have encountered!), but let me give you just a few interesting results:

  1. PPP significantly reduced the tumor burden in the 5T2MM model. Up to 75% reduction in serum paraprotein.
  2. PPP reduced the accumulation of myeloma cells in the spleen by 70%.
  3. Mice treated with PPP survived 180 days…compared to the 100 days of the untreated ones.
  4. PPP also inhibits angiogenesis (good news for us).
  5. PPP may have a direct effect on osteoclast formation and osteolysis. It inhibits osteolytic lesions, a colossal problem in myeloma, as we know.
  6. The study concludes that blocking IGF-1R signaling with the receptor inhibitor PPP not only has a strong antitumoral effect in MM but also has a significant impact on the BM microenvironment, a key contributor to MM tumor expansion.

Let me point out that there are a couple of previous studies on the myeloma-picropodophyllin issue: a 2006 study (full text: http://tinyurl.com/yakrvy6) that I haven’t had the time to read yet, but that concludes that PPP targets the IGF-1RTK, blocks the IGF-1R function in vitro and in vivo, reduces tumor burden, and is associated with prolonged survival and this in the absence of apparent in vivo toxicity

The same edition of “Blood” has a study by the same group of researchers (full text: http://tinyurl.com/ydcqfl8), which comes to the same conclusions. I would like to highlight that PPP also decreased the levels of survivin and mcl-1, among other things.

I have more (strong) thoughts on this topic, but that is fodder for a separate post. Stay tuned!

IGF-1 and multiple myeloma. Part I.

This is not an easy topic. Therefore, I am going to divide it into two parts. In the first, I will make a feeble attempt to provide a brief description of IGF-1…focusing mainly on what it means for myeloma patients. In the second part, I will bring up a couple of things that we can do to give it a big whack…

IGF-1 stands for insulin-like growth factor 1. As its name implies, its molecular structure is similar to that of insulin, but its main purpose is not to decrease blood glucose levels but rather to stimulate the growth of normal cells (IGF-1 affects almost every cell in the body, I read)…and also–and here we get to the crux of the matter–the growth and survival of cancer cells.

Why am I interested in this growth hormone? Well, because in May I read a “Blood” abstract (see below), which showed that there is a connection between IGF-1 and myeloma cell proliferation…and this is not a super recent discovery, by the way. If you do a PubMed search, you will find studies on this issue that date back to the 1990s.

For instance, a 2000 French study (full study: http://tinyurl.com/ybwyngc) tells us that an important mediator of bone remodelling, IGF-1, has been shown to stimulate the proliferation of human myeloma cells. The researchers add that the mechanism involved is still a mystery…but after all, understanding the intricate workings of this process does not matter one whit to me…heck, I probably wouldn’t understand it anyway!

What matters to me is that there is a connection between IGF-1 and myeloma cell proliferation and survival, as we can read in a more recent (2008) study (abstract: http://tinyurl.com/kmbqcs): IGF-1 and IL-6 promote the proliferation and survival of multiple myeloma cells.

Sherlock (grazie!) sent me the full study, from which I took the following excerpt: the IGF-1 receptor (IGF-1R) is universally expressed on multiple myeloma cells, and higher expression levels are correlated with poorer patient prognosis. Okay, I admit that I merely skimmed the text, in part because I don’t have a huge amount of time, but also because this is an extremely complicated technical study, the splitting-headache kind….I finally had to set it aside and give up, at least for now.

Anyway, if you need more convincing that IGF-1 is bad news for us, here is the abstract to a May 2009 study published in “Blood”: http://tinyurl.com/ydl95ye Of the five myeloma growth factors (or MGFs) examined, IGF-1 was the major one…even worse, if possible!, than our old archenemy, IL-6. And here is a bad bit concerning prognosis: Of the investigated MGFs and their receptors, only expressions of IGF-1R and IL-6R in multiple myeloma cells (MMCs) of patients delineate a group with adverse prognosis. Ouch.

I should note that IGF-1 isn’t all bad. It is essential for normal growth and development (but of course we aren’t kids anymore!)…and I also found a study showing that it had a beneficial effect on cardiomyopathic hamsters: http://tinyurl.com/y99h3yo

Okay, but, in the case of multiple myeloma, high levels of IGF-1 = a bad thing. Clearly.

That’s it for today. More tomorrow, providing I can finish my research for Part II…

Last but not least: sweet little Jaymun, you hang in there! (see Jaymun’s journey)