A blog reader (thanks!) alerted me to the existence of a recently-published study on Brassica rapa, which is more commonly known as field mustard or turnip mustard. In Italian, cima di rapa. Luckily, it happens to be in season now, so yesterday I bought some (see photo showing Piccolo munching on one of the stems…) at a farm cooperative conveniently located close to the company where I teach English…

We ate it last night, tender leaves and all–lightly steamed, with the addition of garlic, red pepper (capsaicin!), olive oil and lemon juice. Yummy!

Okay, let’s get back to our study. Here is the link to the abstract: http://goo.gl/rlMHN Now, there is no mention of myeloma in the abstract or the full study, but, as the title of today’s post states, arvelexin, which is extracted from Brassica rapa, inhibits many of the main survival (etc.) mechanisms of myeloma cells, including IL-6, TNF-alpha, NF-kappaB and IL-1beta. Speaking of which, let’s not forget that IL-1beta is closely involved in the progression from SMM to MM, which is why we (smolderers) must closely monitor our CRP levels…According to my most recent tests, my CRP is the lowest it has been in ages…much lower than it was in 2005 (=the pre-curcumin period)… 🙂

Okay, I am looking at the full study now. The introduction tells us that Brassica rapa has been traditionally used to treat hepatitis, jaundice, furuncle and sore throats. Oh, and one of the flavonoids contained in B. rapa is quercetin, which is part of my daily protocol…not coincidentally, I would like to add!

Well, well, well, and lookie here: arvelexin has antifungal activity. Hah!

Without going into too much detail, the main point of this study is that arvelexin inhibits many of the pro-inflammatory genes that are regulated by NF-kappaB, one of myeloma’s bestbestbest buddies. And that is why I predict that a few years from now (at the most) we will come across a study showing that arvelexin kills myeloma cells…Mark my words…

In conclusion…Eat turnips! 🙂

Many thanks to a blog reader for this link: http://goo.gl/SDZ87 Hmmm, I wonder what these lovely creatures were thinking? 🙂

The last post I wrote about Nigella sativa, = a “cure for every disease except death,” dates to May 2008 (see my page on “Black cumin” http://margaret.healthblogs.org/other-alternative-treatments/nigella-sativa-black-cumin/ )…

Back then, there weren’t any scientific studies on Nigella sativa and myeloma…Nonetheless, I was fascinated by, and devoted two posts to, this extraordinary medicinal plant, also known as black cumin, because its main active compound, thymoquinone, had been tested (with very good results) against many types of cancer cells, including pancreatic and super aggressive prostate cancer cells. These tests have shown that thymoquinone blocks many of the signalling pathways that are involved in myeloma. And that is why I was absolutely certain (almost 3 years ago) that it would have an effect on myeloma cells. But I had no proof at the time…

Well. Today. I. Do. Have. Proof.

A blog reader (thanks!!!) recently sent me the link to a study published in October in the “British Journal of Pharmacology” (http://goo.gl/L4kTf), showing that thymoquinone (TQ, from now on) can kill myeloma cells…ruthlessly…

As we can read in the abstract, TQ inhibits STAT3, a crucial signalling pathway that keeps our myeloma cells healthy and alive. Sifting through the rather complicated jargon used in the abstract (and in the full study, I would like to add!), the main point is that TQ has a very strong effect on a lot of the bad stuff in myeloma—cyclin D1, Bcl-2, Bcl-xL, Mcl-1, survivin and VEGF…(I have written about all of these bad thingies…You can do a “search” of my blog if you want to know more…the search box is on the right-hand side…just keep scrolling down my Pages…).

The abstract informs us that TQ also significantly potentiated the apoptotic effects of thalidomide and bortezomib in MM cells. But what I found most interesting is that this compound KILLED myeloma cells on its own, without the help of any other substance…In more scientific terms, it “induced apoptosis in myeloma cells.”

Apoptosis is an interesting and important cellular process also known as “programmed cell death.” I have written about it before (again, use the “search” box)…but, essentially, after a cell is born, it floats around for a while and does whatever it is it is supposed to do…then, when its time comes, it dies. That is what happens under normal, healthy circumstances…In fact, I read somewhere that in just ONE year we can lose half our body weight in cells that have died due to apoptosis = a fascinating titbit that stuck in my mind…

But cancer cells don’t like the “dying” part of the equation. They want to live forever…and so they bring into play a variety of “avoid-death-at-all-costs!” mechanisms. The little buggers even become chemoresistant…

Now, getting back to myeloma cells, one of these survival mechanisms includes STAT3…And that gives us an idea of how important it is to block this pathway when treating myeloma…

I have read the full TQ-MM study, and I must say it is impressive…though it is also quite difficult to follow here and there. As you know, I have a new policy of not quoting directly from copyrighted material…but, hmmm, let’s see…in addition to what we know from the abstract, here is a bit more info…

For those who are more technically-inclined: TQ inhibits the IL-6-induced STAT3 and also Akt activation. It also inhibits NF-kappaB activation, which is the Cruella Deville of myeloma…And it also blocks IL-6, which helps myeloma cells proliferate and build resistance against chemo drugs, among other things. Well, let me assure you that these are extremely positive findings…

The authors conclude that TQ merits further study, since it could possibly be used in cancers linked to the infamous STAT3 signalling pathway. Hah. No kidding!!!

I definitely need to order some more Nigella sativa…yup…

P.S. Interesting Science Daily article on thymoquinone and aggressive prostate cancer: http://goo.gl/cghDV

What a scare I got early this morning! Happy fooling, indeed…except this time, I was fooled!  😉 

Here is what happened: after stumbling downstairs in a half-asleep fog, feeding the cats and drinking a cappuccino (yes, in that order…anyone who has cats will know what I mean…purrfectly…hehe), I did what I always do: I logged onto my blog. And whoa…talk about an eye-opener! Three blooming ads, one about snoring remedies (helloooo???!), were staring at me from my April Fools’ post. Agh! I immediately tried deleting the ads, but nothing worked (at this point, I should mention that I am the least technical person on the planet…I mean, even a toad in Costa Rica could do more with a computer than I can). Desperate to get rid of the #@*&%?! ads, I simply deleted the post. But no, oh noooo…the ads simply floated down to my my pamidronate post! Double-aaaaagh!

After writing to the Healthblogs manager (because of the time difference between Europe and the U.S., though, she is asleep right now), well, I don’t remember how I did it, but I went into the inner workings of my blog and somehow, yes, I fixed the problem. By myself. Amazing! If you knew me, you’d be amazed, too. 😉

Here is my “deleted” and now retrieved April Fools’ post, by the way:

I have just enough time this evening to post a link to two of the BBC’s best April Fool’s Day hoaxes ever: http://goo.gl/Wk6DX (This might be my briefest post ever, too! 🙂 ) Enjoy!!!

This morning a blog reader/friend sent me a newly-published Italian study containing the FINAL results of a trial testing intravenous pamidronate (Aredia) on 177 asymptomatic (SMM) patients. The results are very interesting…you can check them out here: http://goo.gl/2HWNV

According to the abstract, after a follow-up period of 5 years, 55 out of 88 patients in the no-pamidronate, or no-PAM, group had progressed to active myeloma…compared to 56 out of 89 patients in the PAM group. The median time to progression (note: as you read this post, please keep in mind that not ALL of these patients progressed to active myeloma…) was about the same for both groups, with, it seems to me, a very slim advantage, not statistically significant, for the control group.

Let’s see…the only really noticeable difference is that the control group had more skeletal involvement at the time of progression: 72.7% compared to 39.2%. That isn’t good, of course. In spite of that positive finding, however, the authors conclude that the administration of pamidronate in asymptomatic myeloma, while reducing bone involvement at progression, did not decrease the risk of transformation and the time to progression into overt myeloma. Indeed…

Random thought: what if the control group had taken curcumin instead of taking…nothing? There is a growing pile of scientific evidence that curcumin hinders the process of bone destruction (= it inhibits osteoclastogenesis, in more scientific terms). I have actually written a few posts on this topic (scroll down my Pages and look for “curcumin and bone loss”), but I see now that I need to update that information. A quick glance at PubMed this morning, in fact, confirmed that, since I wrote those posts, many other studies have proved curcumin’s activity against those little bone-gobbling buggers called osteoclasts…

Let’s get back to today’s topic. I have read the full study but, as I have recently stated, my new blog policy is not to quote directly from any copyrighted material…However, if I find something helpful or important for us patients in a full study…well, you can finish that sentence. 😉

The idea behind this study: bisphosphonate therapy has been shown to reduce skeletal-related events and pain in patients with active myeloma. The authors therefore wanted to see if it could also be beneficial to asymptomatic myeloma patients, in spite of the fact that, as they themselves point out, three previous clinical trials testing bisphosphonate use on SMM patients had failed. However, since the follow-up of the previous studies was too short, they decided to monitor a group of asymptomatic myeloma patients for at least five years…

Well, it turns out that their longer-term study does nothing but confirm the results of the three shorter-term studies…that is, there is NO BENEFIT in administering bisphosphonates to asymptomatic patients. Sure, there were fewer adverse skeletal issues in the PAM group at the time of progression, but there was no impact on progression to active myeloma or overall survival…Hence, the authors do not recommend the administration of PAM to asymptomatic patients…at least, on the basis of current findings…

Now, a couple of things popped into my head as I was reading this study. One is that it would have been amazingly interesting and perhaps useful to compare a group of SMM patients receiving PAM to another group receiving curcumin. What would the results have been? 

Another thing: I would also have been very curious to know the vitamin D levels of the patients in both groups…but I am sure that they were not tested. Sigh.

On that note, I would like to end with a plea…that some day soon the International Myeloma Working Group, or IMWG, will make vitamin D testing mandatory for all MM, MGUS and SMM patients, mainly based on the findings of a 2009 Mayo Clinic study: the vitamin-D-deficient myeloma patients in this study had worse outcomes than patients with normal vitamin D levels (see: http://goo.gl/sa28p), which reminds me, arrrrggggh!, that I forgot to take my vitamin D this morning!

A couple of days ago, a blog reader (thanks!) sent me a link that started me on a serious case of the chuckles . I mean, is there ANYTHING curcumin can’t do??? See: http://goo.gl/D96Ca

Come to think of it, this recent finding could come in handy in certain situations…Uhm, let’s say you get distracted by a cat fight in the kitchen and, instead of your daily supplements, you swallow something like…uhm…like a bit of black gunpowder or even some nitroglycerine…or how about a stick of dynamite?

Well, no worries! Now we know what to do! 🙂

(P.S. Er, obviously, I do NOT recommend swallowing explosives…It’s a joke!)

A blog reader (thanks!!!) sent me a couple of links that started me off on a unexpectedly startling and, in the end, rather confusing search mission. Who’d have thought that aspirin, = acetylsalicylic acid, might possibly be a bad thing for myeloma patients to take? (Please note my use of the conditional tense.) I concluded that it would probably be a good idea to write a post on this topic for two main reasons: 1. aspirin is currently being tested in more than a couple of myeloma clinical trials (check www.clinicaltrials.gov) and 2. there are more than 50 aspirin-myeloma studies in PubMed…

What does aspirin have to do with myeloma? The answer may be obvious to some, but it wasn’t to me…not immediately, anyway. It is because of aspirin’s blood-thinning properties. It’s because aspirin interferes with our blood’s clotting action, which is good, of course, if we are taking a drug that could cause potentially fatal blood clots, such as thalidomide. And, in fact, if you look at the clinical trials, aspirin is being given to patients on thalidomide or its derivatives. Okay, now we can keep going…

The first link led me to this letter, written by Dr. Kast and published in “Blood” in 2006: http://goo.gl/e1ZVn Here we learn that aspirin and other COX inhibitors have a long documented history of increasing the circulating levels of tumour necrosis factor-alpha…What what whaaaaaat? I didn’t know that. What I did and do know is that TNF-alpha is a major GROWTH FACTOR for myeloma cells…not quite as bad as IL-6, but most definitely one of the really really bad guys… 

Dr. Kast suggests that TNF levels simply be monitored in myeloma patients who take aspirin as part of their therapy. Should their TNF levels increase, he writes, then steps to reverse that elevation or alternative thrombosis prevention measures should be taken. That sounds reasonable…but let’s keep reading…

The second link took me to a 1996 study, published in “Immunology”: http://goo.gl/mrgsV This study examined the effects of aspirin and ibuprofen not just on TNF-alpha but also on other myeloma growth and survival factors such as IL-6 and IL-1 beta. By now I think all myeloma patients must be familiar with IL-6. As for IL-1 beta, well, among other things, it is implicated in the progression from SMM to MM, so those of us with asymptomatic myeloma (SMM) should pay particular attention: http://margaret.healthblogs.org/life-with-myeloma/what-is-multiple-myeloma/myeloma-supplements-and-il-1-beta/).

The “Immunology” study is available for free online and is quite easy to read (just click on “complete article” and wait until it downloads). The gist: a few weeks after a group of healthy volunteers had stopped taking their daily aspirin and ibuprofen doses, their IL-1 beta and TNF levels had increased compared to the pre-experiment period.

Another bad thing that happened is that IL-2, = another pro-inflammatory cytokine, also increased quite a lot. Two observations, though: 1. some sort of different stimuli were used in this study, and I am not entirely sure what that means (I would need more time, more time than I have right now, to check out all this stuff…); 2. the study was published 15 years ago, so it is a bit dated…Still, since I found the data a bit alarming, I decided to do a bit more digging…

I found two other 2006 studies on this topic. I couldn’t find any more recent (than 2006) studies, I mean on the possibly dangerous consequences of using aspirin in conventional myeloma treatments, which I found very odd, but I might have missed a study or two. Anyway, let’s begin with the first, which is, again, available for free online and starts off from Dr. Kast’s above-mentioned letter: http://goo.gl/FgkV8

Let’s look at a couple of key sentences: aspirin, according to these authors, may, in fact, have positive effects on survival in patients with MM. […] Malignant plasma cells often overexpress cyclooxygenase 2 (COX-2) and this overexpression has been found to be a predictor of poor outcomes in MM patients. A few paragraphs later, we read that aspirin inhibits both COX-1 and COX-2 and this may serve as a rationale for possible antineoplastic properties in MM.

The authors then refer to a study they carried out in 2005 (this full study is also available for free (yaaay!): http://goo.gl/ryG3S) on myeloma patients following the DVd-T regimen and divided into three groups. The group that took aspirin apparently had a better response than the group that did not. And so the authors conclude: While these preclinical and clinical observations suggest that low-dose aspirin may have antineoplastic properties in patients with MM, they are not definitive and render the alternate hypothesis (that aspirin has a deleterious effect on the survival of patients with MM) much less likely.

Dr. Kast, author of the above-mentioned “Blood” letter, wrote a response, titled “Aspirin, TNF-alpha, NFkB, and survival in multiple myeloma: the importance of measuring TNF-alpha”: http://goo.gl/RXfoU The abstract tells us that there are conflicting reports on aspirin. On the one hand it has been shown to slightly increase survival duration in multiple myeloma, which obviously is a good thing…on the other, caution is raised about use of aspirin and COX inhibitors generally in inflammatory states and specifically in myeloma. Should they increase tumor necrosis factor-alpha they could exacerbate disease. Exacerbate disease, eh? Well, we certainly do not want that!

At this point, I should announce that, even though I have read the full study, my NEW BLOG POLICY is NOT to quote directly from any copyrighted material. That doesn’t mean that I will stop reading full studies, of course, and reporting on any important bits…I just won’t use direct quotes, that’s all. So I can tell you that Dr. Kast concludes that the use of aspirin in myeloma conventional treatments is okay, provided that TNF levels are monitored, particularly should TNF levels increase together with myeloma progression…

I would also like to mention that, according to Dr. Kast’s review of the scientific literature on this topic, the data is conflicting. Aspirin, and similar COX inhibitors, he writes, can either delay or accelerate myeloma progression…Confused?

Okay, let’s see if we can figure this out.

• First point: TNF-alpha is overexpressed in myeloma, which basically means that it is being produced in larger quantities than needed, and that is a bad thing, since TNF-alpha helps myeloma cells survive, as we have seen.
• Second point: aspirin increases the levels of TNF-alpha. Dr. Kast reminds us that TNF levels go up as myeloma progresses…hence, lowering TNF may delay progression. That makes sense, right?

Well, it’s not that simple. Since 1996, different studies have shown that aspirin decreases, increases or does nothing to TNF levels. No kidding. Frustrating, eh?

So where does all this leave us? Well, just to be on the safe side, I will never take any aspirin again (UPDATE 2017: I have changed my mind on this matter, based on other readings, and I will take, and indeed have taken!, aspirin when needed). More importantly, if I were doing chemotherapy AND taking aspirin to counter any possible clotting problems, I would have my docs monitor my TNF levels frequently and carefully. Or I might ask for a different something-or-other to prevent the clotting…

You never know…

Sometimes Stefano and I dream of moving far away from Florence…

We simply get sick and tired of all the traffic…of the pollution…of how expensive it is to live here…of the horrendous heat during the summer months (never ever visit Florence in July or August…mark my words)…

But then (as we did yesterday evening, on our way back home from walking through a Tuscan nature reserve) we stop at the Piazzale Michelangelo, which has the best panoramic views of the city, and we realize that it would be difficult for us to move away…

Florence still takes our breath away…

Recently, I have seen lots of Italian flags hanging from apartment windows in celebration of the 150th anniversary of Italy’s unification. But yesterday evening, while enjoying the view from the Piazzale, my glance fell on the, er, rather unusual flag here on the left. How original, eh! 

A quick mention, off topic: I am working on about a million different posts (well, okay, slight exaggeration, there!), but mostly I have been celebrating my good test results by taking some time off…spending it with Stefano or in my garden, planting bright, cheery-looking flowers…having fun with my girlfriends (well, and of course my day job takes up a good chunk of my time…).

Research can wait…yes…until tomorrow…

Nope, not R O L A I D S. 😆

No. You spell it as follows: S T I L L  S T A B L E.

That’s right. This morning I finally received my February test results (one of Ingrid Michaelson’s songs, “Keep breathing,” has been my theme song in the past week or so, as you can imagine…ooooof!: http://goo.gl/o8Qby). About time, eh! But last Thursday was a national holiday in Italy–the celebration of the 150th anniversary of Italy’s unification–which affected mail deliveries here…

Anyway, let’s have a look at these results. I have to admit that I expected them to be terrrrible, since I still had a bit of a cough/chest infection (=aftermath of the flu) when I went to the lab last month…but I am happy, for once! (hehe), to say I was wrong!

Let’s start with the not-so-good results: my white cell count has dropped slightly below the normal range: 4.1 (should be at least 4.4). My WBC is the only slightly bad number in my hemochrome, though. Everything else is just peachy…My haemoglobin is even up a wee bit. Oh wait, this is supposed to be an overview of the NOT-SO-GOOD results, Margaret… 😉

I knew that my total IgG would be highish, and so it was. It went from 3360 mg/dL to 3790. I actually expected it to be higher, since, I repeat, I was still a bit convalescent. But, as we will see in a sec, this is no big deal in the end…

Another not-so-good result, okay, a rather bad one: my vitamin D dropped to 27.1 from last year’s 78.9. Oh, snore! Here I should mention that I stopped taking vitamin D in May 2010 when my levels went above the normal range. I didn’t take my vitamin D supplement all summer, in fact, figuring I was getting enough sun…hah. Evidently, I wasn’t! In the fall, I began taking my vit D supplement again, but not on a regular basis…So this nose dive was my own silly fault...

Of course, there is a remedy: from now on I will take vitamin D religiously every morning. This vitamin D drop,  which, incidentally!, might explain why I got such a bad case of the flu early last month, also means that my parathyroid hormone has shot back up to 94…UFFISSIMA! 👿  At the most, my PTH should be 72 pg/mL. However, I am not concerned about this result, either, since my vitamin D intake should bring it down again…

Uric acid: 6.1. That’s a bit high. Now, this number has never gone above the normal range before, so this is a bit of an odd result. I checked my creatinine levels, which are fine, even though they went up ever so slightly (but still way within the normal range)…Hmmm, oh well…next time, it will be lower, for sure.

Okay. Enough. Now for the GOOD stuff! And yes, as you can imagine, there is quite a bit of that. I plan to go down the list, item by item, in order not to miss anything, so what follows is not in order of importance:

My ESR levels dropped from 93 to 36 mm/hour. Why, that is ALMOST normal!!! I checked previous blood tests, and my ESR hasn’t been that low since I progressed to SMM (= in 2005). Celebrate!

Total protein: down slightly, from 9.8 to 9.5.

Beta-2 microglobulin: from 2.6 to 2.4.

C-reactive protein: from 0.23 to 0.09. The lowest it has been in a looooong time.

UPDATE (oops, forgot to put this in yesterday). Calcium: down to 8.9 from 9.4. 🙂

Bence Jones: negative.

IgA and IgM, still holding at 14 and 10 (mg/dL), respectively. My little heroes…

Albumin, now in the normal range: 4.65.

Gammaglobulin is down ever so slightly: 3.09 from 3.12 g/dL. 

M-spike: down from 2.98 to 2.92. Yes, again, this minuscule drop is nothing to get overly excited about, but hey, I am thrilled that it has gone down, not up! True, all the above numbers have barely changed at all, but all those itsy bitsy fluctuations are going in the right direction, which is just FINE and DANDY with me! Indeed, I think it’s time now for a little dance of joy (to Sara Bareilles’ “King of Anything”: http://goo.gl/ZaEga)…

Back to us: everything else shows no change, hence my conclusion that I am stable…

Still stable, after all these years…trallallerotralalà!

For the past couple of days, whenever possible, I have been working on what I consider to be an important post, but today I simply couldn’t deal with it (one of the studies is driving me bonkie bonka bonkers), so I decided to take some time off and have a quick look at the Clinical Trials website…and wowwowwow!, I made some interesting discoveries, one of which I will share with you immmmmmediately…

This link http://goo.gl/zO7b8 will take you to a clinical trial testing the theory that omega 3 supplementation might prevent MGUS and SMM folks from progressing to active myeloma…How about THAT? But wait a sec…how did I NOT know about this trial?!!! Hmmm. Well, better late than never…right?

Let’s see, I already take two grams of fish oil/day…and if it weren’t so late in the day, and if I didn’t have to hurry so that I can catch the 8 PM news about Libya and Japan, I would (try to) calculate my EPA/DHA ratio compared to the trial’s ratio…Oh well…tomorrow…

This, by the way, is a Phase II trial, which is performed on a larger group of people once the safety of the substance/drug being tested has been ascertained in a Phase I trial…And it is still recruiting…

Now, I don’t suppose any of you would happen to be in this trial and wouldn’t mind posting a quick report or whatnot, eh? 🙂