Finally, my June 26 test results! The reason it took so long to get them is that I wanted certain vitamins etc. to be tested. Normally, you get your test results in two weeks. My mother, who is cat-sitting for us back in Florence, read them to me over the phone a short while ago.

In a nutshell, my MM is still stable. My IgG has indeed increased from 28.8 to 30.6, BUT most of the other markers have improved, in some cases remarkably so. For instance, my blood viscosity has halved. No kidding. It’s still not within the normal range, but it’s going in the right direction, and that’s what matters. My platelet count has gone up from 262 to 283, which is also good news. My albumin went up a bit, so now it is even more within the normal range. And my monoclonal component went down one entire percentage. Yippee! Total protein and my other immunoglobulins (low, as to be expected), no change; my calcium is down slightly, still way within the normal range.

Okay, not everything is shining and bright and glorious. Since my April tests, my ferritin has gone from 11 to 7 (the normal range is 15-200 ng/ml), which is abysmally low. So I will have to eat some red meat (sigh!) and other iron-rich foods, otherwise I fear that my hematologist will tell me to take iron pills. I should note, though, that my serum iron is way within the normal range, and there is no big change in my hematocrit and hemoglobin. My Beta-2 went up slightly compared to my April tests, from 1.5 to 1.7, but is still way within the normal range, which is 1.2-2.5 mg/L. Those are really the only two “bad” values.

I had wanted to test resveratrol between April and June, but I ran out of resveratrol capsules at the end of May or thereabouts, and the new shipment I was expecting from the U.S. in May was stopped by Italian customs (by the way, the shipment arrived safe and sound…about three weeks ago! Oh well…better late than never). So I ended up not testing any new substance but just taking my usual daily dose of curcumin, quercetin and oil capsules. Therefore, all in all, these results are quite satisfactory. Sure, I would have preferred a huge IgG decrease, but after all, as this Italian proverb wisely states, chi s’accontenta, gode (I found this translated as: “well pleased is well served”). Right? 🙂

The next couple of days we will be helping my husband’s uncle and aunt a fare i pomodori, or “do the tomatoes.” 100 kilos of tomatoes in all. This is an ancient tradition that is still observed in central and southern Italy in particular. Quite an experience, similar to participating in a vendemmia or grape harvest (I have done that, too, but I was a bit younger then!).

The process is simple: you put on some old clothes (at the end of this process, they will be completely splattered with tomato juice and seeds, so you don’t want to be wearing your good Ferragamo suit 😉 ), wash the tomatoes and leave them to drip a bit, then you slit them in half, squeeze out some of the seeds and pulp and toss the inspected and approved tomatoes into a cauldron (see photo). Each one of us has to make sure that all the rotten tomatoes get discarded. The seeds and tomato juice are later poured onto the compost heap, so anything useful gets recycled. It is a very efficient system, but also a lot of hard work, I assure you (my back is killing me right now!). However, in the end the families that still follow this tradition have enough homemade bottled tomatoes to get them through the winter months. And doing the tomatoes with the right group of people can be a lot of fun. As it was today. There were only five of us at work this afternoon: the two of us, Stefano’s aunt and uncle, and a 6-year-old niece, as cute as a button and full of beans. I know, it sounds a bit like child labour, but I assure you that for her it was all a big game. And besides, this is how traditions get passed on to the next generation. Anyway, we chattered and laughed and teased one another and had a jolly good time. In less than two hours we filled 7 cauldrons, which have now been put into the wood oven (see photo) to cook overnight. We will process those tomatoes tomorrow morning, when we will also prepare another huge batch of tomatoes that will be boiled, passed, bottled and sterilized. There should be a few more family members helping us tomorrow. I say, the more, the merrier (and the more laughter and the more gossip to be heard)!

I have known about this extract for more than a year, but haven’t posted about it yet. This, by the way, was the non toxic anti-MM substance I mentioned in my previous post. Anyway, even though (starting today) I am officially on my summer holiday (bliss!), I happen to be alone for a little while this morning…with access to a computer, Internet and all of my research data! Too much to resist. 😉 So I decided to write a quick post about this plant extract, even though it deserves more than a passing mention. At any rate, what follows is a tiny part of what I have found, the part that concerns MM, specifically.

Parthenolide (PTL) is a sesquiterpene lactone €”in simple terms, that is a chemical that can cause an allergic reaction, see http://tinyurl.com/2p67dh €”extracted from a daisy-like plant called feverfew (Tanacetum parthenium), a medicinal herb that belongs to the sunflower family. Feverfew has been used in European traditional medicine to treat headaches, arthritis and digestive ailments, and also to reduce fevers and relieve menstrual pain. But more importantly, its active component, parthenolide, has been found to kill various cancer cells, including pancreatic, breast cancer, acute myelogeneous leukemia cells, and, ah yes, MM cells.

A 2006 study published in Apoptosis (http://tinyurl.com/2dv39g) explains that PTL has anti-inflammatory, anti-microbial and anti-cancer properties, and also activates the tumor-suppressor p53 and inhibits NF-kappaB and STAT-3. Excellent! Thanks to a good friend (grazie!), I have the full study in my possession. In addition to all the above, PTL also induces intracellular oxidative stress, which is manifested by elevation of reactive oxygen species (ROS) levels and activation of c-Jun N-terminal kinase (JNK). Because of the induction of oxidative stress, the researchers conclude that PTL works in a similar manner to Bortezomib, which I thought was quite interesting. In the end, they report: We here demonstrate that an active component of medicinal plants, PTL, induces apoptosis in four different MM cell lines, and the concentrations required for its proapoptotic effect are less than those that induce toxic effects in normal lymphocytes and hematopoietic BM cells. Our results encourage the belief that PTL can be applied clinically in the chemotherapeutic strategy for these MM cells. Another 2006 study (in Chinese, but the abstract can be read in English: http://tinyurl.com/26jzbz) also examined the effect of PTL on MM cells. Apoptosis was again the result.

Now, there is a reason why I have not written a post about PTL until today, in spite of its anti-MM effects: it is a blood-thinner. Since I already take curcumin, I am wary of adding another blood-thinner to my daily intake. But I do have a listserv friend whose SMM has been stable for years, and PTL is on his A list of supplements. So who knows? Perhaps some day I will have the courage to stop taking curcumin for a couple of months in order to test parthenolide. Not any time soon, though.

I have lots more to say, but my time is up now. I have to get back to my holiday. 😉

I was going to post some of my research on yet another non toxic anti-MM substance today, but that will have to wait because this morning I read a bit of interesting news about rosacea. As I have mentioned in a previous post, I have this facial skin disorder, which used to bother me a lot but now troubles me much less. Having cancer can give you a different perspective on things that used to matter, like appearance. Not that my appearance doesn’t matter to me, but you know what I mean! Anyway, I read this morning that 14 million U.S. citizens have rosacea. That is not just a handful of people, is it? This condition can have a real effect on your social and professional relations, as exemplified in this excerpt from the National Rosacea Society’s homepage: In recent surveys by the National Rosacea Society, nearly 70 percent of rosacea patients said this condition had lowered their self-confidence and self-esteem, and 41 percent reported it had caused them to avoid public contact or cancel social engagements. Among rosacea patients with severe symptoms, nearly 70 percent said the disorder had adversely affected their professional interactions, and nearly 30 percent said they had even missed work because of their condition. So, you see, having rosacea is no fun. It’s a real nuisance. I confess that I still put on a bit of makeup when I go to work; the rest of the time, I simply forget about it. Just about anything can trigger a flare-up: heat, cold, any change in temperature, stress, exercise, spicy foods (so I have read, at any rate, but that is not my case), embarrassment, and probably coffee. Concerning the last item, I have regular flare-ups after drinking my morning coffee. But hey, what is a little redness compared to the pleasure of drinking a glorious hot cappuccino first thing in the morning? 🙂

But let me start approaching the point of my post. What causes rosacea? The National Rosacea Society’s homepage states that the cause is unknown. And in fact, in the past, whenever I tried looking this up, I’d find heaps of could be this and could be that, but nothing conclusive. Until today. A study, titled Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea and published in the August issue of Nature Medicine, has apparently identified THE CAUSE: an overproduction of two interactive inflammatory proteins leads to excessive levels of a third protein that makes your face turn as red and blotchy as that of an adolescent. (Indeed, I have always wondered if my MM could be connected to this chronic inflammatory condition.) The study has been published so recently that I was unable even to locate and read the abstract. However, I read several online news reports providing enough details, so for now that should suffice. The two above-mentioned overactive proteins are called SCTE (stratum corneum tryptic enzymes) and cathelicidin, which under normal circumstances protect the skin from getting infected etc. But it turns out that we rosacea folks have higher levels of these proteins in our facial skin than regular folks. And these two proteins happen to be the precursors of the rosacea-causing peptides, which are small proteins present in our immune system. Too much of one thing can be harmful, I guess (unless, of course, the “thing” is chocolate! ;-)). However, this (in a way!) is great news. It means no more antibiotics, no more antibiotic creams (which never seemed to work anyway), because rosacea apparently is NOT caused by bacteria but by an overzealous immune system response. So if we can manage to inhibit these enzymes/proteins/peptides, whatever you want to call them, we should be all set. Oh wait, I just read that H. pylori is implicated in the development of rosacea. Well, well. So my research is not even half-finished. And what if wait a sec!, let’s see: rosacea may be caused by an excessive immune system response and may be linked to H. pylori, which in turn may be linked to MGUS hmmmm, ok, I need to connect a few of these dots but this is enough for today.

Today, by the way, is my parents’ 53rd wedding anniversary. How about that? Congratulations, Mom and Dad! I love you!

Tomorrow Stefano and I are going off on our summer holiday (we will be in southern Italy, near Naples). We will be gone for two weeks, but I will still have access to the Internet, my blog and e-mail. I probably won’t be posting much, other than holiday photos but after all a holiday is a holiday. 😉

A close Italian friend of mine has borderline MGUS-SMM. With every test, her markers go a bit up, then a bit down, then a bit up. It has been this way for years: she was diagnosed with MGUS when she was in her early 20s, and she is now in her early 50s. She and I have a completely different approach. I want to know every little detail about MGUS, SMM and MM. She has never wanted to know and still doesn’t want to know. And I am beginning to think that she was right, in the sense that she has managed to avoid, in her own way, all the stress that accompanies a diagnosis like this one. She knows, of course, that it is important to have blood tests done every six months, and she follows her hematologist’s advice. But that’s it. She has never had any conventional treatment for her MGUS, nor has she followed any alternative treatments. And she has done, and is doing, very well.

My friend is a competition-level swimmer. She belongs to a team, consisting of swimmers her age who travel all around Europe participating in competitions, obviously not at the Olympic level, but still serious stuff. I am writing about her today because a couple of weeks ago she travelled to Southern Italy, where she and other 28 swimmers from all over Italy (also one German and a couple of French swimmers) participated in an extraordinary non-competitive swim across the Strait of Messina, which is a ribbon of water (3.3 kilometers, slightly more than 2 miles, in its narrowest point) between Sicily and Calabria. This is not an easy swim: the currents are very strong and treacherous. Nor is it a simple event to organize: all sorts of permits must be obtained in order for swimmers to make this crossing. The usual heavy ship traffic through the Strait must be stopped, for instance, and each swimmer must have a boat following her/him. And so on. Of course, these rules exist for the safety of the swimmers. And at the end there are no prizes, no, not even one little award. The swimmers participate in this competition just for the fun of it.

Well, I am happy and proud to report that my friend swam across the Strait in less than one hour (apparently and luckily, that particular day the currents were not so strong) and arrived first in her group. Yesterday, while we were playing cards with another close friend of ours, she told us about the crossing, how absolutely amazing it had been. The water was, or seemed!, crystal clear, the day was perfect, one of her team members saw a swordfish, and she never panicked, even though she had never attempted anything this dangerous. 29 people swimming across the narrow channel that divides Sicily from mainland Italy: what a spectacle that must have been. I am sorry I was not able to be there!

Yesterday I asked her (jokingly, of course): “So, what’s next, the Atlantic?” Her reply: “What’s to stop me?” What, indeed? 🙂

I am about to leave to go play cards with my girlfriends and eat ice cream!, but I thought I first would post a joke, sent to me recently by a friend (thank you!). It gave me and my parents a giggle. 🙂 Here goes:

Morris and his wife Esther went to the state fair every year, and every year Esther would say, “Morris, I’d like to ride in that helicopter.” Morris always replied, “I know, Esther, but that helicopter ride is fifty dollars, and fifty dollars is fifty dollars.”

One year Esther and Morris went to the fair, and Esther said, “Morris, I’m 85 years old. If I don’t ride in that helicopter, I might never get another chance.” To this, Morris replied, “Esther, that helicopter is fifty dollars, and fifty dollars is fifty dollars.”

The pilot overheard the couple and said, “Folks, I’ll make you a deal. I’ll take you both for a ride. If you can stay quiet for the entire ride, I won’t charge you one cent! But if you say just one word, it’s fifty dollars.” Morris and Esther agreed, and up they went. The pilot did all kinds of fancy maneuvers, but not a word was heard. He did his daredevil tricks over and over again, but still not a word. When they landed, the pilot turned to Esther and said, “By golly, I did everything I could to make you yell out, but you didn’t. I’m really impressed!”

Esther replied, “Well, to tell you the truth, I almost said something when Morris fell out, but you know, fifty dollars is fifty dollars.”

A lot of interest on the MM listserv concerning cyclopamine. Rightly so, I might add. I am still poring over the scientific studies dealing with this topic, but some of the jargon is beyond my “translating” abilities. So this will take a bit of time (which I do not have, at present!). However, I did find out a couple of things, which may be of general interest.

1. cyclopamine is very expensive: one gram costs $ 5,000. I would be happy to provide more info to anyone interested (the company name, etc.). It appears that cyclopamine is sold in a powder (?) form, since there are warnings on how to store and handle it (wear gloves and a mask, etc.);

2. initially, the MM listserv member tested cyclopamine together with Revlimid and Dexamethasone (the latter: pulsing, every 4-5 weeks). He reports, though, that his M-spike had not decreased on the latter two drugs, which by then he had been taking for seven months. However, when he added a daily dose of 200-300 mg of cyclopamine (mixed in water) for ten days, his M-spike went from 0.9 to 0.4-0.5. His most recent self-administered cyclopamine test lasted 15 days, again at 200-300 mg/day. At that point he added lovastin, a cholesterol-lowering drug. The lovastin-cyclopamine combination, by the way, was tested in a research trial at Johns Hopkins (see the January 2007 Johns Hopkins press release: http://tinyurl.com/2m92jg). When administered together, they killed 63% of brain cancer cells; when used separately, that number went down to less than 20%. At any rate, on this combo, the list member’s M-spike went down to 0.3, and is now down to 0.2. Of course, as with curcumin (in my case), it is difficult to say whether or not it is the cyclopamine. My bet is on cyclopamine, though.

Anyway, the cyclopamine studies and the MM list member’s reports, are very promising. Yes, cyclopamine costs an arm and a leg, but taking out MM by its roots has always been my dream, and this may well be another (non toxic) step in the right direction.

This morning a MM listserv member reported on something that he has been taking for the past two months called cyclopamine. I’d never heard of it before, or perhaps hadn’t paid any attention to it, so I looked it up. Well, this may be one of the most exciting things I have read about in recent times. I still have some (a lot of?) research to do, but I thought I would post some preliminary findings. I still have to read all of the following studies carefully when I have more time. Not today.

The remarkable story of how cyclopamine was discovered can be read in the following 2005 article published in Forbes: http://tinyurl.com/yu6df5 In a nutshell: in the 1940s and 50s, one-eyed lambs were being born on a farm in Idaho. During an 11-year investigation conducted by the U.S. Dept. of Agriculture, it was discovered that the farm’s sheep were grazing in fields of corn lilies, flowers that contain a poison (later called cyclopamine ) that does not harm adult animals but does cause birth defects. The Forbes article provides many more details, also about how cyclopamine later came to be of interest to cancer research. Fascinating. Cyclopamine was found to inhibit a gene known as Sonic hedgehog, which is involved in the process of adult stem cell division and apparently is crucial for the development of MM, pancreatic cancer and other cancers. For more info on the importance of hedgehog pathways and MM and other B-cell malignancies, please see this July 2007 study: http://tinyurl.com/2g6kk6.

A team of researchers at Johns Hopkins made the connections between cyclopamine, the Idaho lambs and the hedgehog gene. Their findings were published in 2002 in Genes and Development (http://tinyurl.com/38vppa). A few years later, in 2006, a Stanford study published in PNAS tells us that the hedgehog signalling (or Hh) pathway is crucial for the proliferation of MM stem cells. Well, lo and behold, cyclopamine inhibits that pathway: http://tinyurl.com/2hx5yd.

As I mentioned, I have been able to glance only at the conclusions of all these studies, but plan to read them carefully soon. My time has run out, but I did want to post quickly about this bit of extraordinary news. If we can get rid of our cancer-making stem cells, we can kill off the remaining cancer cells with curcumin or resveratrol or whatnot. How about that? A couple of final questions (and this is another reason why I need to do more research!): how come cyclopamine targets only cancer stem cells? Why doesn’t it target non-cancerous stem cells as well?

Last year, for months I mixed curcumin powder with all sorts of fat concoctions (coconut milk, flaxseed oil etc.), in an attempt to find a palatable one. No matter how careful I was, the bright yellow powder seemed to end up on, and stain!, every surface in my kitchen–my white kitchen counter, my black and white male cat (whose white paws turned yellow and stayed yellow for weeks), and everything I wore, including two of my good white cotton turtlenecks. After the first week, I learned my lesson, duh!, and began wearing dark clothing and a black apron. I also handled the powder over my stainless steel sink, not over my kitchen counter (I had to use bleach to get rid of the yellow stains on the counter). At any rate, I thought the clothing stains would be permanent, since turmeric is used as a dye in India. Hmmm, well, I may have been wrong. Perhaps those stains will finally come out.

Yesterday, in fact, I read a Boston Globe article written by Dr. Knowledge (two physicists from Northeastern University, actually). Dr. Knowledge tells us a few things that we already know, that turmeric contains more or less 5% of its active ingredient, i.e., curcumin (5 to 8%, as far as I know), and that curcumin dissolves in oil and alcohol but not in water. And that, the physicists say, is why water will not get rid of curcumin stains. In fact, they say, if you put some curcumin powder and some water in a bottle and shake it, the water will not turn yellow but remain pretty much clear, but if you shake a bottle containing curcumin powder with oil or alcohol, you will end up with a bright yellow/orange mixture. I have actually tried doing that, and it is true! So, what about those stains?

Why does turmeric create such stubborn stains, and how can they be removed? Boston Globe. July 23, 2007

[ ] This leads to the first thing you can do to try to get curcumin stains out — try using alcohol or oil. Of course you then need to get the alcohol or oil out which you can do by flushing with water (in the case of alcohol) or washing with soap or detergent (in the case of oil). Curcumin is also fairly unstable in the presence of ultraviolet light, so you can “bleach” out the stain by leaving it in bright sunlight. You may also have some luck with bleach, but if you’re worried about damaging colored fabrics, the sunlight trick can be a good one.

By the way, you can read the full text of this Globe article at: http://tinyurl.com/yqouto I am going to try these remedies. Can’t hurt! Good luck with your curcumin stains, if you have any! 😉

Remember the movie Sex, Lies and Videotapes ? I saw that years ago, and rather liked it, as I recall. Oh, but here I just wanted a catchy title for my post, which actually has nothing to do with either sex or lies, but concerns MyD88, which is an intracellular signaling protein that carries signals from pathogen-associated molecules (translate: biological agents that can cause disease and illnesses, like parasites and viruses and bacteria) to IL-1, an inflammatory cytokine. Wikipedia defines MyD88 as: a universal adapter protein as it is used by all TLRs (except TLR 3) to activate transcription factor Nfkappa B. What are TLRs, you may ask? They are toll-like receptors, or proteins that play an important role (cytokine activation, for instance) in the immune system. I know, I know, this is not easy for me, either! But please bear with me. I do have a point or two to make. And at times I am swimming in very deep (very scientific!) water so if I make a mistake, please let me know.

Why am I writing about MyD88 today? Well, yesterday, as I was looking at the July 2007 issue of Science, my glance fell on this title: Sex, Cytokines and Cancer (http://tinyurl.com/2sq9v6). I must admit that if that article had been titled, e.g., MyD88 and Cancer, I probably would not have been intrigued enough to read it. What can I say? I too like to have a bit of fun with catchy titles, as you may have noticed 😉

The first part of the article deals with the relationship between cancer and inflammation. It’s an interesting read, so I urge you to go have a look. The authors then examine two studies, published in the same issue of Science. The first, by Naugler et al (see: http://tinyurl.com/237wfb), discusses the link between gender and liver cancer, and the fact that estrogen is an IL-6 inhibitor, which I did not know. The second, by Rakoff-Nahoum and Medzhitov (http://tinyurl.com/2bu9nr), is a study on intestinal cancer. These two researchers discovered that MyD88 stimulates the overexpression of COX-2 and of IL-1, suggesting that this protein promotes and also thrives on cancer. Well, I looked up IL-1 and discovered that it happens to be a MM cell growth promoter, as can be seen in this 2006 Oncogene study: http://tinyurl.com/2wp4sb Indeed, according to another 2006 study (http://tinyurl.com/3294yj), published in the Journal of Interferon and Cytokine Research, IL-1 it is a potent inducer of the important myeloma growth factor, IL-6. This particular study, which compared groups of SMM and active MM patients with low or high IL-1 production, was interesting for another reason. The researchers found that when IL-1 was inhibited, the production of IL-6 in most patients dropped by 90%, leading them to the conclusion that it may be possible to predict patients that will progress to active MM and to delay or prevent this progression with IL-1 antagonists.

DELAY or PREVENT progression? My dream come true!

At this point, a flickering light bulb went on in my head, and I looked up MyD88 and curcumin. Sure enough, curcumin apparently prevents this protein from going about its nasty business. A July 2007 study (http://tinyurl.com/33cjlc), published in the Journal of Leukocyte Biology, discusses bacterial infections and curcumin, and concludes that curcumin inhibits the MyD88-dependent and -independent signaling pathways of LPS signaling through TLR4 [ ]. LPS, by the way, stands for lipopolysaccharide, an endotoxin found inside pathogens (bacteria, e.g.), and TLR4 is another of those above-mentioned toll-like receptors (see Wikipedia for more information on TLRs: http://tinyurl.com/3demwz). A June 2006 study published in Biochemical Pharmacoloy (http://tinyurl.com/2tvjnu) shows that curcumin inhibits both MyD88- and TRIF-dependent pathways in LPS-induced TLR4 signaling. (Note: TRIF, or TIR-domain-containing adapter-inducing interferon-β, is a signalling pathway that is active mainly in the spleen and is dependent on MyD88.). Oh, and by the way, curcumin downregulates the expression of IL-1, too. A more detailed discussion can be found in Prof. Aggarwal’s 2006 study titled “Spicing Up of the Immune System by Curcumin,” which I would be happy to forward upon request.

I also discovered that EGCG has the same blocking effect of curcumin against MyD88 (see: http://tinyurl.com/2lrh8r): green tea flavonoids can modulate both MyD88- and TRIF-dependent signaling pathways of TLRs and subsequent inflammatory target gene expression. Now how about that? All this makes me wonder how many more non toxic phytochemicals can inhibit MyD88 ? When I have more time, I must look into this matter more carefully.

Concluding remarks. For the non-scientists among us, this appears to be gibberish, but the basic point is that here we have a couple of non toxic substances €”curcumin, EGCG €”that inhibit the activity of a protein, MyD88, essential for the activation of NF-kB. No MyD88, no NF-kB. It seems to be that simple! So if we can block the activity of this signalling pathway, we can also block the effect of inflammatory cytokines that are important, indeed, crucial, for MM cell proliferation and survival. This tiny bit of research (and I barely revealed the tip of the iceberg, there were more studies to be had on this topic, but unfortunately my time is extremely limited today) has given me another reason to keep taking curcumin, and to add EGCG to my future supplement list.