In a recent “Blood” Table of Contents I read that a link has been established between pesticide exposure and MGUS. A team of researchers examined a select group of participants in the Agricultural Health Study, which began back in 1993. They determined that, compared to a control group, these farmers faced twice the risk of developing MGUS. In the study abstract (http://tinyurl.com/mjpcrh) we can read that exposure to pesticides has previously been linked to excess risk of multiple myeloma, albeit inconclusively. Well, you can take a look at the abstract on your own; I will focus only on the full study (grazie mille, Sherlock!)…

 

…from which I will take a few excerpts, such as the following: Although the cause of MGUS and multiple myeloma remain [sic] largely unclear, previous cohort and case-control studies have reported an elevated risk of multiple myeloma among farmers and other agricultural workers. More specifically, pesticides (ie, insecticides, herbicides, fungicides) have been hypothesized as the basis for these associations. However, most prior investigations have been hampered by small numbers and limited exposure assessment.

 

The Agricultural Health Study of 57,310 private and commercial licensed applicators of restricted use of pesticides enabled researchers to determine that there was a 1.34-fold […] excess risk of multiple myeloma among pesticide applicators compared with population rates in Iowa and North Carolina.

 

Furthermore, Several pesticides widely used on farms and in homes and gardens by the general public were associated with increased multiple myeloma risk in previous analyses coming from this cohort. Currently, however, it is unclear whether the observed increased risk of multiple myeloma among persons exposed to pesticides might reflect a higher prevalence of MGUS or an increase in the rate of progression from MGUS to multiple myeloma. Unclear or not, this study confirms what we all know or should know: pesticides, insecticides and herbicides are very very VERY bad substances. That is why my entire family eats only organic vegetables…

 

But let’s keep reading. The team of researchers used the Agricultural Health Study to carry out (my emphasis) the first population-based study of MGUS in relation to pesticide exposure in a sample of 678 male pesticide applicators. They discovered that 38 (5.6%) of these workers had MGUS. But read this: nobody under the age of 50 had MGUS…that adds up to a total of 123/678 men. So MGUS was detected only in the older-than-50 group.

 

The team also looked at 50 (!) specific pesticides, of which the worst, in terms of being MGUS risk factors, were: the chlorinated insecticide dieldrin, the fumigant mixture carbon-tetrachloride/carbon disulfide, and the fungicide chlorthalonil. Further on: Our analyses point to possible links with dieldrin, a chlorinated insecticide, which had a significant 5-fold excess risk of MGUS prevalence, and carbon tetrachloride/carbon disulfide mix, a fumigant, which had a significant 4-fold risk of MGUS prevalence. Holy cat! Other potentially dangerous substances are also mentioned…such as Permethrin, a commonly used insecticide that has been linked to multiple myeloma, another insecticide called chlorpyrifos, and two herbicides—atrazine and glyphosate.

 

The researchers conclude that (again, my emphasis) several million Americans use pesticides for which we have found an association with MGUS in the Agricultural Health Study. Some of these same chemicals have been associated with excess multiple myeloma risk. […] Future studies are needed to improve our knowledge on the role of pesticide exposure in the pathogenesis of MGUS, as well as the potential role in progression from MGUS to multiple myeloma.

 

I am almost 100% positive that this is the first study to link MGUS to exposure to commonly used insecticides, herbicides and so on. This bit of news is rather unsettling, to say the least. By the way, if you use any toxic stuff in your garden and would like to have a look at the Table listing the various substances tested (more than 30), drop me a note.

 

After reading this study, I am sooo glad that our garden is completely organic. Sure, we are bothered by weeds, but we don’t use herbicides; we simply do a bit of weeding whenever possible. Weeds are annoying but they can’t kill us. And yes, our garden has been invaded by pests of all sorts, from tiny aphids to big snails, but we have never used insecticides to get rid of them. We either use nothing at all, or, when things get really bad, I make up a spray bottle with natural homemade mixes. True, this way we lose a certain number of raspberries and figs and whatnot, but so be it. I would rather be safe than poisoned!

I do have a confession, though: every spring for the past few years, I have periodically used a Bayer ant spray to keep ants from marching through our house…it releases a sort of smelly foamy poison (I am now too scared to check the active ingredient…!) that is supposed to create an anti-ant barrier for three months. Now, since I have used that insecticide only in recent years, I know it didn’t cause my (former) MGUS. Even so, I am now seriously thinking of taking up Cathy’s suggestion to use corn meal instead! I also just did a quick online search and found heaps of helpful suggestions on natural non-toxic ways to keep ants from becoming too bothersome. I am going to try a few of those…and from this day forward, there will be no more toxic poisons in or around my house!

Link to the Agricultural Health Study: http://aghealth.nci.nih.gov/index.html

I haven’t had very much time to do research these past few days, but I did want to post the link to an article about two recent laughter studies, see:  http://tinyurl.com/lye6gw I have already posted about the importance of avoiding stress (because of the connection between stress and myeloma cell proliferation)…but these studies give us a few more good reasons to laugh laugh laugh and…laugh!

And the beneficial effects of laughter are apparently long-lasting–up to 24 hours after watching a funny movie. 24 hours!, wowie. This article has given me an incentive to find and post more funny stuff and build up my funny page section (see right-hand side of my blog, scroll down to Laughter and MM)…

While working on my, er, upcoming STAT3 post (=in draft mode for months now!), I came across an anti-myeloma substance called butein (see: http://tinyurl.com/lu4jny). It is an active extract of Rhus verniciflua Stokes (and of other plants as well, such as the stem-bark of cashew trees), a medicinal plant that has been used for ages in Asian countries to treat pain, thrombosis, gastritis, stomach cancer and parasitic infections. I also read that it is used as a food additive in Korea, which would seem to guarantee its non-toxicity…

 

In recent years, butein has been found to have anti-proliferative effects on a number of cancer cells, including breast cancer, colon cancer, osteosarcoma, lymphoma, acute myelogenous leukemia, melanoma and hepatic satellite cells. I also found a study on bladder cancer cells showing that butein inhibits the activation of NF-kappaB as well as halting metastasis. (I can provide links to all these studies upon request.)

 

A 2007 MD Anderson study (see: http://tinyurl.com/n5yx9k; click on “manual download” if the automatic one doesn’t work) proves that Butein inhibited the constitutive NF-kB activation in MM cells. These results indicate that butein can suppress not only inducible but also constitutively active NF-kB in tumor cells. (The more I read, the more I like this stuff…)

 

The myeloma-butein study (grazie, Sherlock!) that I mentioned at the beginning of this post was published in “Molecular Pharmacology” in 2009. MD Anderson researchers found that butein inhibited both constitutive and interleukin-6-inducible STAT3 activation in multiple myeloma (MM) cells. Without (yet) going into details about the STAT3 signaling pathway, let me just mention that its inhibition is good news for us.

 

More titbits: butein also inhibits the wicked members of the Bcl family, cyclin D1 and Mcl-1…all of this led to the suppression of proliferation and induction of apoptosis. And also: butein significantly potentiated the apoptotic effects of thalidomide and Velcade in MM cells. In fact, according to these researchers, butein may have the power to reverse chemoresistance in myeloma cells.

 

Because of time constraints, I must jump directly to the results and discussion parts. Note: the researchers tested butein also on prostate cancer and head and neck cancer cells. They found that butein inhibits the activation of STAT3 in these cancer cells as well…both constitutive and inducible STAT3 activation (by the way, the inducible type, which can be caused by icky nasty IL-6, was suppressed 100% by butein in lab tests!).

 

Then we have a long list of butein’s anti-myeloma properties. Impressive, but I decided against posting all these various activities, since that would make my post look like an incredibly lengthy laundry list. Here, though, is an important excerpt: butein significantly enhanced the apoptotic effects of Velcade from 20 to 70% and of thalidomide from 5 to 55%. Well, well…

 

At the end of the study, the researchers argue that the pharmacological safety of butein and its ability to down-regulate the expression of several genes involved in cell survival and chemoresistance and potentiate the effect of Velcade and thalidomide provide a sufficient rationale to further carry out preclinical studies preceding human trials.

 

Hear hear!

Interesting article about resveratrol in a recent Science Daily: http://tinyurl.com/kjzfao

This bit, toward the end, caught my attention…not because of the rather poor phrasing (hehe) but for the content: Resveratrol is largely inactivated by the gut or liver before it reaches the blood stream, where it exerts its effects – whatever they may be – good, bad, or indifferent. Thus, most of the reseveratrol [sic] in imbibed red wine does not reach the circulation. Interestingly, absorption via the mucous membanes [sic] in the mouth can result in up to around 100 times the blood levels, if done slowly rather than simply gulping it down.

Of course, when you really think about it…if drinking red wine improves health, then the above paragraph makes little sense. Resveratrol must be absorbed at some level other than the bloodstream, don’t you think? Well, in any event, it can’t hurt to drink wine slowly, savoring it and swishing it around in the mouth like sommeliers do…

My funniest student, whom I have nicknamed “colleague C” here on the blog, was in a comical mood this morning. We chatted a bit, then began some grammar exercises, one of which required her to put “a, the, or nothing” into each gap. The first sentence in the exercise was: “I come to _____ school by _____ bus.”

She began filling in the blanks: “I come to the school…” Then she paused, peeking up at me. My slight frown indicated that “the” was not the correct answer. So she said “no, I come to a school…,” and again glanced at me. Another frown.

Well, there was only one possible answer left, so she came up with the following gem: “I come to nothing school…” 🙂

Yesterday evening Stefano and I went to see our family doctor, an absolutely brilliant man, knowledgeable in a variety of fields…not just conventional medicine. My admiration for him would fill more than one post, no question about that. But I digress…

He went through my recent test results carefully, comparing them to my November 2008 results. He told us that yes, the monoclonal component has indeed gone up, BUT, he added, if those increased markers go back down again in the fall (as we all think they will), then we can ascribe this to normal lab variation, nothing more. In other words, this increase isn’t high enough to justify any sleepless nights. (Not that I have been having any sleepless nights, mind you. Indeed, I always sleep like a hibernating bear!)

Conclusion: I am still stable. 😀

This morning my endocrinologist prescribed several truckloads of vitamin D for me…the type that will not increase my serum calcium (that would not be a good thing!). She also confirmed that my kidney functions are fine and dandy. Good to know. 

I would like to thank each and every one of you…those who left me public comments and those who dropped me private notes of encouragement. I very much appreciated all your kind and supportive words…and the heaps of suggestions! Paul, your usual stroke of genius. I hadn’t thought of that possibility. Furthermore, after posting my test results, I received a note from one of my blog readers informing me that he had taken the exact same feverfew supplement, for the same amount of time (six months, that is), but took three times the dose that I took. Well, not only did his markers remain stable, but his liver and kidney results were the best he has ever had. Excellent news indeed. So I am definitely not giving up on feverfew. I will give it another whirl…perhaps next fall, after my next set of tests…

In the meantime, this is going to be a great summer! Now please excuse me, Sherlock has sent me a couple of new studies…;-)

A blog reader/myeloma list member (thanks!) sent me some links to cute cat videos. The “cat in a bag” one, hehe, reminded me of how obsessed my own cats, especially Puzzola and Peekaboo, are with boxes and bags…Too funny. Anyway, enjoy!

 

http://tinyurl.com/n2ubxq (cat and a big box)

http://tinyurl.com/mh7y3a (same cat stuck in a small box)

http://tinyurl.com/maxvn6 (same cat with a bag over her silly head)

http://tinyurl.com/nwtllu (different cat, “massaging” a dog)

Today is Stefano’s birthday. After the scare I gave him a few days ago, I thought I’d better come up with something good (!), and this lovely sonnet (Italian and English translations provided) by Pablo Neruda fits the bill perfectly: 

 

Non t’amo come se fossi rosa di sale, topazio

o freccia di garofani che propagano il fuoco:

t’amo come si amano certe cose oscure,

segretamente, tra l’ombra e l’anima.

 

T’amo come la pianta che non fiorisce e reca

dentro di sé, nascosta, la luce di quei fiori;

grazie al tuo amore vive oscuro nel mio corpo

il concentrato aroma che ascese dalla terra.

 

T’amo senza sapere come, né quando, né da dove,

t’amo direttamente senza problemi né orgoglio:

così ti amo perché non so amare altrimenti

che così, in questo modo in cui non sono e non sei,

così vicino che la tua mano sul mio petto è mia,

così vicino che si chiudono i tuoi occhi col mio sonno.

***

I don’t love you as if you were the salt-rose, topaz

or arrow of carnations that propagate fire:

I love you as certain dark things are loved,

secretly, between the shadow and the soul.

 

I love you as the plant that doesn’t bloom and carries

hidden within itself the light of those flowers,

and thanks to your love, darkly in my body

lives the dense fragrance that rises from the earth.

 

I love you without knowing how, or when, or from where,

I love you simply, without problems or pride:

I love you in this way because I don’t know any other way of loving

but this, in which there is no I or you,

so intimate that your hand upon my chest is my hand,

so intimate that when I fall asleep it is your eyes that close.

I got my test results yesterday. Not great. As you read through this post, please keep in mind that my previous tests (excellent ones, by the way) were taken six months ago, in November 2008. Well, I have learned one very good lesson: never again will I wait that long between tests…okay, here goes…

 

My total protein went from 8,6 to 9,5. It’s been above 9 before, but this is the highest it’s ever been.

 

My IgG jumped from 32,80 to 39,90. Ouch.

 

My M-spike went from 2,33 to 2,68. Double ouch.

 

B2M went from 1,7 to 1,9. Not a big concern, since it’s been that high before.

 

I also have a rather scary vitamin D deficiency. My endocrinologist had told me not to take any vitamin D before this set of tests, so I didn’t. Whoah, though. This particular value turned out super low. I need to speak with her and start on a vitamin D supplement ASAP.

 

As soon as I received my results, I sent them to Sherlock who looked them over and then phoned me. These are a few of her very wise (come al solito!) thoughts: perhaps an ingredient in the feverfew extract that I took for six months might have inhibited the anticancer activity of the curcumin. Aha. That is very possible. And her theory might be confirmed by the fact that my (already high) cholesterol went up a staggering 14 mg/dL, which doesn’t make much sense when you think about it.

 

Another possibility, my good friend told me, is that I may have some sort of latent infection. That would explain my high IgG and also my still high ESR (note: my ESR is less than it was in July 2008, which is good). At any rate, Stefano and I are going to talk this over with my family doctor on Monday to see what can and should be done.

 

Let me add that the news was not all bad. For instance, I am definitely not anaemic. My haemoglobin, red and white blood cell count etc. are all fine. My ferritin is up to 13, back in the normal range, yay, and my serum iron continues to be fine. And my other markers have remained more or less the same, for instance my creatinine is still at 0,7, perfectly normal.

 

Let’s see. Now we get to the “big no-no.”

 

Of course we always want our markers to be stable or even better than stable, so any increase is a disappointment if not outright frightening. But I thought I had taken the news quite well…there were no signs of what would happen later on…when Stefano got home from work, that is.

 

I began, “I have something to tell you…,” and then, to my utter surprise and horror, I felt tears welling up in my eyes. Oh no. Not now. I tried to hold them back and managed to continue, “I got my results…and…they…are…really…bbbad…!!!” Then, phoosh!, the deluge…

 

Oh no…my poor husband! Through my tears, I could see the alarmed look on his face, so I managed somehow to reassure him…that he shouldn’t worry, that I was still stable but some of my markers had increased a bit. Phew, relief! This leads me to make the following obvious point:

 

If you ever have some disappointing or worrisome news to break to your caregiver, please try NOT to cry! Not a good idea…mark my words!

 

Well, I obviously have some pondering to do in the next few weeks. In the meantime, I have decided to stick exclusively with what works (no more experimenting!), that is, my daily dose of curcumin/bioperine, quercetin/bromelain and purified fish oil. E basta!

 

Another decision: I won’t fret about these results but will enjoy my summer. No more tests until the fall. And, bloody hell, no more tears!…unless, of course, prompted by a fabulous BBC drama series!