Monthly Archives: February 2009

Pomegranate extract inhibits IL-1 beta

A dear friend (grazie!) sent me a study on pomegranates yesterday morning. In the bibliography, I found a 2005 study (abstract: http://tinyurl.com/dh685b; the full study is free, too) discussing a substance called PFE, or pomegranate fruit extract. The exciting bit is that PFE inhibits IL-1 beta, which, as you may recall, is a key player in the progression from smouldering or inactive myeloma to active myeloma. Hah! (My February 1st and 5th 2009 posts deal with IL-1 beta and its inhibitors.)

 

Since the full PFE study is available online, I won’t bother going into too many details. Just a few notes.

 

Let’s start with a sentence in the abstract: Interleukin (IL)-1beta induces the expression of matrix metalloproteinases (MMPs) implicated in cartilage resorption and joint degradation in osteoarthritis (OA). Okay, so this study doesn’t specifically mention multiple myeloma, but it is still relevant to us. You see, MMPs are enzymes that play a role in bone destruction and neoplastic growth (they contribute to angiogenesis, e.g.). I read that our myeloma cells actually produce MMPs in order to hollow out our bones…at any rate, simply put, MMPs are evil, evil thingies, and anything that inhibits them is good. As is anything that inhibits IL-1 beta.

 

Well, this pomegranate extract fits the bill. It inhibits the expression of IL-1 beta-induced MMPs. Since I love pomegranate seeds and juice in my salads, that is FABULOUS news indeed! Now I am sorry that I didn’t freeze any pomegranate seeds at the end of last summer…ah, bummer!

No “right” way to cope…

As I have written in other posts, back in 2005, after reading the words “mieloma multiplo” on my bone marrow biopsy test result, I burst into tears. Even though I had known for quite some time that my benign condition might progress to malignant myeloma, those two little words punched me right in the stomach. (Note: this was the pre-curcumin era.)

 

Stefano, my husband of almost 10 years now and partner of 13 years, put his arms around me and just held me. I could feel him trembling, so I knew that he was upset, too. But, other than that, he showed no outward emotion…

 

Well, ever since then, I have been worried about him. And, occasionally, believing that it was for his own good, I have quizzed him…how does he feel about possibly losing me to myeloma at some point in the future? Why does he almost always put up an invisible shield and dodge my questions? Why, why, why? “It’s not healthy for you to keep your emotions bottled up inside,” I would say to him. And that is what I thought…until yesterday.

 

That is when I read a Science Daily article (http://tinyurl.com/ckupne) on how different people cope, differently!, with tragic events. My myeloma cannot be compared to a plane crash, of course, but after reading the above-mentioned article, I feel much reassured about Stefano’s coping strategies.

 

It seems, in fact, that there is no “right” way to cope. If people want to express their feelings openly, like I do, fine. But if they don’t, then it’s not good to force them or make them feel that there is something wrong with not talking “about it.”

 

As a result, I won’t bug Stefano anymore. Er, well, okay…at least, I will try!

Student prankster

Since I am a bit tired right now and don’t feel like doing any research or editing (zzz!), I am going to write about one of my students, a slender man, about my age, with an irresistible twinkle in his eye. Let’s call him Phil. I have been teaching Phil English for about a year and a half, now. Until this morning, though, I had NO idea how dangerous this meek-looking man could be. It turns out that he is an evil prankster. Here are just a few of the practical jokes he has played in the past on unsuspecting victims…

 

Phil’s “criminal” career began early, when he was but a child. For instance, Phil would fill his grandfather’s slippers with icky goo while the dear man took his afternoon nap. You can imagine what happened when, still half asleep, his grandfather slipped his feet into…yuuuck!

 

The adult Phil worked for several years in a leather company in Florence. One of his colleagues was a Ms. Perfect, a prim and proper lady who always wore THE perfect outfit, THE perfect makeup, THE perfect accessories. Never a hair out of place. Well, once, on a rainy day, Phil sprinkled an entire bottle of talcum powder inside her umbrella. After work, she grabbed the umbrella, went outside and opened it…right over her head, as it happened. POOF! A cloud of talcum powder covered her…from head to toe.

 

Another day Phil announced that he was about to get married. A few days later, he showed up at work carrying a wedding cake with a bride and groom on top and also some bomboniere. These are typical Italian wedding “favours,” which consist of five sugared almonds symbolizing health, wealth, happiness, fertility and long life. The almonds are usually placed inside small tulle or organza sachets together with some stupid little trinket.

 

The bomboniera tradition is still alive in Italy, although the useless, and expensive!, trinkets are being replaced, thank goodness!, by contributions to charitable organizations. But almonds are still offered to wedding guests. img_9647Before Stefano and I got married, we spent HOURS putting together our bomboniere, counting the almonds, putting them inside the sachets, adding tiny fake flowers and trying to tie the tiny little ribbons…Can you tell that I believe that certain traditions should be abolished??? Except that some of the sachets that I have collected over the years (why on earth have I kept them???) and was attempting to photograph just now provided a certain amount of entertainment for Peekaboo, as you can see…by the way, our wedding “trinket,” a ceramic spoon rest made by a potter friend in the United States, can be seen in the foreground. We wanted it to be useful, at least.

 

At any rate, Phil did such a good job of tricking his colleagues into believing that he had gotten married that he was showered with wedding gifts for days. Hmmm, I forgot to ask if he returned them…

 

Another story. One of Phil’s colleagues kept a milk carton in the fridge for his morning caffelatte. One day, Phil carefully opened a brand new carton, finished off the milk and filled the empty carton with water. He then sealed it back up again. And waited…

 

The following story finally convinced me that Phil (I am quite fond of him, you see) has an evil streak. One day, Phil opened another colleague’s container of plain white yogurt. He ate or got rid of the yogurt, then filled the empty container with white glue and sealed it up again. After lunch, the unsuspecting colleague opened his yogurt, sniffed a spoonful and declared, “y’know, Phil, this yogurt really smells a bit ‘off.’” I forget exactly, but I think he may have tasted it just to be sure…

 

I have vowed never to let Phil within a few metres of the fruit juice that I take to work…

It’s not the Coliseum, but…

img_9573Well, actually, it’s not an amphitheatre. This morning Stefano and I went to visit the Roman theatre in Fiesole, an ancient hillside town that offers a spectacular view of Florence on a clear day…not today, though…today was very hazy…oh well.

Stefano had (incredibly!) never been inside the archaelogical park in Fiesole, and I hadn’timg_9596 been there since liceo (high school), so it was fun and new for both of us.

The 3000-seat theatre, built in the year 80 BC, still hosts concerts and art exhibits and so on. It’s worth a visit, for sure. Here are a few of the photos I took.

First, a panoramic shot of the amphitheatre. The second photo shows a view of the archaeological area seen from the arches of the Roman baths. You can make out the bell tower of the Cathedral of Fiesole beyond the arch on the left.img_9643 The third photo offers a view of what is left of the Etruscan and Roman temples. 

Ah yes, a lovely day.

Yikes!

Stefano and I spent our August 2008 holiday in Bourgogne, France. We had a wonderful time there, visiting quaint Medieval villages, picking and eating blackberries on country lanes, drinking lovely pinot noirs and chardonnays and enjoying the region’s rich selection of cheeses and foie gras…now wait a sec…FOIE GRAS? Impossible, no, not Margaret the animal lover. She wouldn’t!

Well, uhm, in fact, er…she did.

I confess: I ate some foie gras last August for the first time in my life. We bought a terrine from a small local producer at a colorful street fair in one of those quaint villages. Yes, I know how foie gras is made…I know. I know! I don’t think I could have felt guiltier if I had tasted some roast puffin…gee wiz. Guilt, guilt, guilt.

Why am I writing about this today? Why in the world am I fessing up to eating a bit of foie gras…several months ago? Well, because I just finished reading this Science Daily article and am still in shock: http://tinyurl.com/af9wnr Eeeek!

This excerpt is particularly horrifying: “Stressed poultry birds are known to undergo spontaneouseek amyloidosis due to a chronic inflammatory response that causes amyloid fibrils to form non-functioning deposits of this protein-like material in their organs.”  Spontaneous amyloidosis???  

Pâté de foie gras is apparently the only type of “food” that contains “high levels of amyloid fibrils and no demonstration of it affecting people has been seen.” Still…no more foie gras for us. Never ever again. For many MANY reasons…

Yes we…cat!

Cats can talk: http://tinyurl.com/2gjoqe

…solve your printer problems: http://tinyurl.com/56tzof

…help you learn new computer tricks: http://tinyurl.com/ysjozr

…exhibit human-like behaviour (my male kitty does this, too!): http://tinyurl.com/bdzorf

…babysit your…pet rat: http://tinyurl.com/a7wx2t

…adopt all sorts of abandoned baby animals: http://tinyurl.com/6qhlo8
and http://tinyurl.com/bnok9l

And finally, a heartwarming dog (with cancer) story…http://tinyurl.com/bvylpb

The cure versus control debate

S. Vincent Rajkumar, MD, of the Mayo Clinic, wrote a very interesting article last fall about the cure/control issue (see: http://tinyurl.com/aham3e). Two fundamental questions: Should we treat patients with myeloma with multidrug, multitransplant combinations with the goal of potentially curing a subset of patients, recognizing that the risk of adverse events and effect on quality of life will be substantial? Or should we address myeloma as a chronic incurable condition with the goal of disease control, using the least toxic regimens, emphasizing a balance between efficacy and quality of life, and reserving more aggressive therapy for later?

The ensuing paragraph confirms that there is no cure for myeloma. Ok, we already knew that. What we have instead is what is called “complete response” or CR. Now, I should note that quite a few studies have demonstrated that CR is not relevant for the vast majority of myeloma patients in terms of overall survival (see, for instance: http://tinyurl.com/bbjkuh). And Dr. Rajkumar essentially seems to agree: Cure vs control is debated because the strategies currently being tested are not truly curative but rather are intended to maximize response rates in the hope that they will translate into an operational cure for a subset of patients. Not very encouraging…

Dr. Rajkumar then provides a history of myeloma’s conventional treatments. CR was rare before the 1990s. Back then, Cure was never a goal of therapy because it was assumed to be unattainable. The goal was instead to control myeloma and keep the patient alive for as long as possible with a minimum of toxic side effects.

Then, in the 1990s, he writes, high-dose therapy with autologous stem cell transplant (ASCT) became part of standard practice when it was found to prolong survival compared with conventional chemotherapy. There follows a list of the conventional drugs that we myeloma folks know well, from thalidomide to bortezomib. Dr. Rajkumar states that the results have been remarkable and that curing rather than controlling myeloma has become the goal of many specialists.

He adds, though, that it is not uncommon to find that well-meaning investigators interpret the same clinical trial data in opposite ways because they ascribe to different philosophies (cure vs control). Hmmm, so the same data can be interpreted in more than one way…this statement makes a good case for getting a second opinion, if not a third and fourth, before making any decision regarding treatment. Eh.

Then we get to the first important statement (from my point of view): It is far from clear whether increasing or intensifying therapy for patients without CR until such status is achieved actually prolongs overall survival. In other words, although the achievement of CR is a favorable prognostic factor, modifying therapeutic strategy with the sole purpose of achieving CR in a patient who is otherwise responding well to therapy is of unproven value. Precisely.

Dr. Rajkumar then makes a series of very good points, which you can go read for yourself. I will simply highlight a few:

  • in clinical trials, CR is often but not consistently associated with better overall survival.
  • trying to achieve the highest CR rate may cause harm […]. High CR rates frequently require more aggressive, more toxic therapy.
  • a small monoclonal protein (minimal residual disease) is not in itself clinically important and is commonly present in the general population in the form of monoclonal gammopathy of undetermined significance. In many patients, reduction of myeloma to a state similar to monoclonal gammopathy of undetermined significance (near-CR or very good partial response) may be all that is required for best long-term survival.
  • CR in myeloma, unlike CR in large cell lymphoma, reflects profound tumor reduction but not elimination of the clone and thus is not a true surrogate for cure.
  • achievement of a CR seems particularly important in the 15% of patients with high-risk myeloma, whereas survival is similar in patients without high-risk features who have and have not achieved CR.

A question popped into my head as I was reading this article: how many patients do poorly for the rest of their lives or die as a result of the harsh CR-type therapies compared to those who actually achieve CR? Dr. Rajkumar makes no mention of this…yet there must be statistics…

There follows a discussion on stem cell transplants, both autologous (using one’s own stem cells) or allogeneic (using a donor’s stem cells). Interesting.

I was curious to know Dr. Rajkumar’s personal opinion. Outside of a clinical trial setting, he prefers the more cautious approach, the “control” one…except in a few high-risk cases. He implies that this approach gives more decisional power to the patient (I am so glad to know that Dr. Rajkumar does not follow the “Dr. House” approach to treating patients! P.S. I watch “Dr. House” even though sometimes it makes my blood pressure soar…).

Well, I am with Dr. Rajkumar. My motto is “primum non nocere.” Since the more toxic approach is not curative…why subject your body and spirit to it? It just doesn’t make any sense, that is, unless your myeloma is aggressive, unless you are a high-risk patient, unless nothing else works…

And, while we are at it: why in the world would you choose to have chemotherapy if you are MGUS or stable SMM, without any CRAB symptoms? Does it make sense to get your myeloma cells all worked up and possibly more aggressive? Especially given that, and I repeat Dr. Rajkumar’s words (see above list), In many patients, reduction of myeloma to a state similar to monoclonal gammopathy of undetermined significance (near-CR or very good partial response) may be all that is required for best long-term survival. Indeed.

Unless we have a stubborn and aggressive type of myeloma, there are heaps of things we can do to delay or even stop (hey, why not shoot for the moon? 😉 ) the progression from inactive to active myeloma. I have suggested many scientifically-backed approaches right here. So have a few blog readers. Whatever works…

Just my opinion…as usual.

Sherlock

I haven’t mentioned my good friend Sherlock (I’m Watson, of course!) in a while. Well, the reason is simple. Back in November (2008), she decided to see what would happen if she stopped taking curcumin for a few months, whereas I decided to test feverfew.

 

[Note: I still haven’t had my blood tests done, for a variety of reasons. A lot of folks here have the flu, which means that the hospital lab is filled with dreadful coughers…and why do they always end up sitting next to me in the waiting room? 😉 ]

 

At any rate, I admit that in the past I too have been tempted to stop taking curcumin, just to see if my markers would remain stable. Last spring, I even asked my haematologist what she thought about my forgetting about curcumin for a couple of months. To my utter surprise, she told me that it would not be a wise move at all. Well, if she says so…!

 

So, back in November, just as I began my feverfew experiment, Sherlock ended her daily curcumin intake. She continued to take fish oil capsules, and I seem to recall that she also took Zyflamend (I could be wrong about that). She caught a chill in early January and came down with a terrible cough and sinus infection. She told me that she hadn’t been that ill in years and wonders if it could be because she stopped taking curcumin, which is both anti-viral and antibacterial. That could well be. Anyway, she went through three cycles of different antibiotics, poor dear.

 

She finally had blood tests done in early February 2009, 5-6 days after finishing her last cycle of antibiotics. She still had the remnants of a cough, though, as I recall, and that is something to keep in mind as we look at her test results (below), which, by the way, she authorized me to publish. I won’t bother mentioning any markers that more or less remained the same.

 

Compared to her October 31 2008 tests, her February 3 2009 tests are as follows:

 

·        ESR went from 26 to 69.

·        Calcium, from 9.1 to 10.1.

·        Uric acid, from 3.7 to 4.3.

·        Total protein, from 8.1 to 9.4.

·        Her CRP went from <1 to <9, so there must have been an increase of some sort. I would like to note that is extremely annoying to have such an inaccurate reference range for CRP.

·        M-spike, from 2.42 to 2.76. Her m-spike has never been this high.

·        But her monoclonal component went from 29.9 down to 29.4. Go figure.

·        A good thing: her IgM went from 0.17 to 0.23. But her IgA went from 0.11 to 0.10, and her IgG, probably because of her recent illness, was on the high side; it went from 31.30 to 35.50 g/L.

 

Ah, one more rather interesting number: her haemoglobin didn’t increase that much during this period (remember that curcumin is an iron chelator). It went from 12 to 12.3. Almost no variation.

 

So, how to interpret these results? Not easy. Sherlock believes in curcumin almost as strongly as I do (and began taking curcumin again right after having these tests, incidentally). These February results, however, don’t seem to prove much, in my opinion. In spite of the slight increase in m-spike and whatnot, she still seems to be more or less stable, which of course is excellent. Matters might have been different if she had stayed off curcumin for at least six months AND her markers had continued to worsen. But she stopped taking curcumin for only three months. Plus, the illness, the antibiotics, the lingering cough…hard to say…but any thoughts are welcome, as always!

 

Final comment: Sherlock is fine, now. That’s the important thing!

 

P.S. I haven’t been doing any research, answering e-mails or blogging lately. I apologize. It hasn’t been an easy period…I have been distracted by some not-so-good family news. One of Stefano’s relatives has just been diagnosed with inoperable pancreatic cancer. He is 40 years old and has a 4-year-old son. I am still in shock, as is the whole family. And my mother-in-law has also not been well. Quite the opposite, in fact. Nope, this has not been a good period. Still isn’t. But we are all trying to be optimistic…the glass is still half full, not half empty…and life goes on…yes indeedy.

Clock gene slows cancer growth

Don (Myeloma Hope blog) has recently been discussing chronotherapy, or chrono-modulated therapy, in which the chemo is administered at the time of day that takes advantage of a person’s biorhythms to maximize the benefit and minimize the side effects of the drug (see http://myelomahope.blogspot.com/2009/02/plateau-continued.html).

 

It just so happens that I just finished reading a Science Daily article (http://tinyurl.com/dykr6y) linking the disruption of the circadian clock, the internal time-keeping mechanism that keeps the body running on a 24-hour cycle, to the slowing down of cancer growth. Coincidentally, more than a year ago I wrote a post about our complex internal ticking system (see my November 11, 2007 post; great set of comments, too). The subject is of huge interest to me, since it would be absolutely fantastic to figure out the best time of day to take supplements…

 

At any rate, a team of University of North Carolina researchers discovered that genetically altering one of four essential “clock” genes actually suppressed cancer growth in a mouse model commonly used to investigate cancer. A group of mice with a mutated p53 gene (p53 is a tumour suppressor under normal circumstances) lived longer, 50% longer!, when the researchers fiddled around with their internal clocks. Their experiment showed that the mutation of this clock gene reactivates the intracellular signals that can eliminate cancerous cells. Well, well…

 

So the idea would be to slow down the rate of cancer progression by altering the internal clock of those who possess the p53 mutation. And, since this mutation is present in about 50% of human cancers, that would be quite an impressive number of patients. Hmmm, question: how do we find out if we have a mutated p53 gene?

At any rate, The findings could enable clinicians to reset the internal clock of each cancer cell to render it more vulnerable to attack with chemotherapeutic drugs. Reset e-a-c-h cancer cell? Uhmmm…hey, Scotty, beam me up!

Seriously now, more research is needed (I know, I know, I say that a lot, then I get totally sidetracked into researching heaps of other things…oh well…). I have begun compiling a list of circadian studies…at this rate, with all the studies I have to read, let’s see, uhm, I will have to live at least another 120 years…hey, I wonder if I can reset that part of my biological ticker…!