Blood. I went to have my blood tests at Careggi hospital this morning. From now on, my friend and I are going to try to have our tests done at the same time, depending on our schedules etc. This morning, chatting about this and that, time simply flew by, and we were out and having breakfast in a nearby café by 8:15 a.m. or so. However, since I had requested that certain minerals (magnesium, etc.) and vitamins (B12, etc.) be checked, I discovered, to my horror, that I won’t have my test results until the end of July-beginning of August! I guess I won’t be holding my breath…

Zyflamend. Talk about coincidences. After reading one of Dr. Benelli’s books on curcumin and other NF-kB and COX-2 inhibitors, I looked up holy basil and read about Zyflamend, which is a blend of various herb extracts. Well, right there and then I decided to order a two-month supply, which my parents (who live in the States) are bringing to me this summer. And here is the coincidental part: just yesterday I came across a recently published study by Prof. Aggarwal and others on this polyherbal mixture: http://tinyurl.com/2ppxf7 Among other things, Zyflamend was found to inhibit NF-kB, down-regulate COX-2 and suppress osteoclastogenesis. Well, well. I know, I have broken my vow not to post about brands on my blog, but this bit of news was too good to keep to myself. Here is the list of herb extracts contained in this product: Rosemary (leaf), Turmeric (rhizome), Ginger (rhizome), Holy Basil (leaf) extract, Green Tea (leaf) extract, Hu Zhang (Polygonum cuspidatum) (root and rhizome) extract, Chinese Goldthread (root) extract, Oregano (leaf) supercritical extract, Baikal Skullcap (Scutellaria baicalensis) (root) ethanolic extract. This blend comes so close to my idea of putting different anti-MM plant extracts into a bioavailable capsule…

Capsaicin. Ever since reading about capsaicin and MM (see my page on this topic), I have been adding hot red pepper to my food. But I have an exciting update. Prof. Aggarwal, the magnificent Dumbledore of scientific research, recently co-authored a study concerning the effects of capsaicin on the STAT3 pathway in human MM cells. The “Clinical Cancer Research” May 2007 abstract can be read at: http://tinyurl.com/2xy88n. I am hoping to access the full study soon. At any rate, here are a few excerpts (practically the entire abstract…!): We found that capsaicin inhibited constitutive activation of STAT3 in multiple myeloma cells. [ ] Capsaicin also inhibited the interleukin-6-induced STAT3 activation. [ ] Capsaicin down-regulated the expression of the STAT3-regulated gene products, such as cyclin D1, Bcl-2, Bcl-xL, survivin, and vascular endothelial growth factor. Finally, capsaicin induced the accumulation of cells in G(1) phase, inhibited proliferation, and induced apoptosis, as indicated by caspase activation. Capsaicin also significantly potentiated the apoptotic effects of Velcade and thalidomide in multiple myeloma cells. When administered i.p., capsaicin inhibited the growth of human multiple myeloma xenograft tumors in male athymic nu/nu mice. It’s almost time for lunch, so pass the capsaicin, please! 😉

This morning, while sipping my usual cappuccino, I watched a trailer from the new Harry Potter movie, which will be in theatres on July 11, and was reminded that the final HP book is about to be published. Oh, no! That will be a very sad day for all of us HP fans, even though I AM looking forward to reading the final chapter of the saga. At any rate, the trailer made me think back to when I mixed curcumin powder with warm coconut milk and pretended to be putting together a health potion in one of Snape’s classes. A bit of this, a bit of that, and poof!, here is the MMCA, or Multiple-Myeloma-Cell-Apoptosis, potion! Now I just swallow capsules, which doesn’t give me the same feeling of power that I had while watching my white coconut milk turn bright orange. Other things that I watched turn orange (permanently, and in blotches) were a couple of my nice white cotton turtlenecks. 😉 No matter. At any rate, I have decided to go back to making my powder potion, my elixir of life, next fall.

Random HP thought: for all you HP fans, I don’t think Snape is bad mark my words.

Tomorrow I am going to Careggi hospital (Florence’s main hospital) to have my blood tests done. I have been procrastinating for a couple of reasons: 1. hope that my resveratrol capsules would be delivered before the end of the month so I could at least try to finish my resveratrol experiment and 2. hope that there would be ONE cool morning in June so I wouldn’t melt while walking across the sizzling hospital parking lot. But even HP magic could not have altered these two facts of life. My resveratrol (see below) is still sitting in a post office warehouse in Milan, and Florence is one of the hottest and muggiest cities in Italy. Therefore, no more procrastination. I am going to meet a close friend (with SM) very early tomorrow morning up at Careggi. We can chat up a storm as we wait for our numbers to be called. After our blood tests, we plan to have breakfast together. Perfect.

Resveratrol package update. The lost package has been found. That’s the good news. The bad news is that I won’t have it for another two weeks, at least. Bureaucracy. I am resigned.

I took the weekend off. Did almost no research. Yesterday morning I got stumped on a little thing called p38. I finally gave up and went off to play cards with my hilarious girlfriends. I will resume my research today, though. So many substances left on my list!

Solid gold, indeed!!! I just finished reading the most remarkable study by an MD Anderson research team on the wonders of curcumin, published in December 2006. It is titled Curcumin: the Indian Solid Gold, and is available online at: http://tinyurl.com/3y767z I was going to write a summary, highlighting what I thought were the most interesting and relevant points, but I was so overwhelmed by the study that I was unable to do so (but I may try again soon). For now, I will simply urge those interested to go read it for themselves. You won’t believe your eyes. Just think: the bibliographic references consist of 974 items listed on more than 60 pages. Impressive. It will take me days to go through them. That’s what summer holidays are for, I guess! 😉

A study published in The New England Journal of Medicine this month (the abstract can be read at: http://tinyurl.com/yweyh9) looks at the risk of progression from SMM (or smoldering or inactive or asymptomatic myeloma) to symptomatic MM or amyloidosis. Digression: have you ever had an amyloidosis test? I have, and I must say that I almost prefer a BMB! For me, at least, that test was horrible. But it turned out that I do not have amyloidosis, so that at least is a relief. Back to us.

Mayo Clinic researchers looked at 276 patients diagnosed with SMM, most of whom had the IgG type, between 1970 and 1995. The patients were between the ages of 26 and 90 (median age: 64). Only eight patients, or 3 %, were under the age of 40. 59% of all patients eventually developed MM. I won’t repeat what is available online (i.e., what’s written in the abstract), but give a summary of some of the more interesting points made in the full study, which I was lucky enough to read. First, following the study’s indications, let me define SMM. A diagnosis of smoldering myeloma is based on the presence of a serum monoclonal protein level of 3 grams (or more) per deciliter, or the presence of 10% (or more) malignant cells in the bone marrow, but no symptoms, such as too much calcium in the blood, kidney problems, anemia, bone lesions (these are also known as the four CRAB symptoms), or persistent bacterial infections. In other words, no end-organ damage. SMM, like MGUS, should not be treated.

The study divided the above-mentioned patients into three groups: group 1 had a proportion of bone marrow plasma cells of 10% or more and a serum monoclonal protein level of 3 g per deciliter or more; group 2, 10% or more bone marrow plasma cells and a serum monoclonal protein level of less than 3 g per deciliter; and group 3, less than 10% bone marrow plasma cells and a serum monoclonal protein level of 3 g per deciliter or more. Based on this scheme, I would be in the second group.

Progression to MM was more likely with a higher level of monoclonal protein 5 grams versus 2 grams/dL “at the time of diagnosis. (Interestingly, factors such as gender, haemoglobin, serum albumin level had little to do with progression.) Median time to progression was two years for those in group 1, eight years for group 2, and 19 years for group 3. The cumulative probability of progression at 15 years was 87% for the 106 patients in group 1 (10% plasma cells and 3 g or more of monoclonal protein per deciliter), 70% for the 142 patients in group 2 (10% plasma cells and <3 g of monoclonal protein per deciliter), and 39% for the 27 patients in group 3 (<10% plasma cells and 3 g, or more, of monoclonal protein per deciliter). Time was found to be of the essence: the more time passed after the initial SMM diagnosis, the better (more details can be found in the abstract). This is a big difference between SMM and MGUS, where time is not a factor.

What do I conclude from all of these statistics? First of all, let me say that, while this is a very interesting study, numbers don’t scare me. Not a bit. Besides, all we know about these patients is that they had SMM. That’s it. No information on diet, supplement intake (if any) and so on. Too much perhaps vital information is missing, here. Understandably so, of course, given the long period of time involved, i.e., 26 years. But still…

Secondly, as I suppose is slightly obvious from my blog 😉 , I am a devoted curcumin-taker, and curcumin has stopped the progression of my MM right in its tracks. My future IgG trend (plotted by my husband on a graph) is finally a downward one. Yet in January of 2006, I would have been in group 1, based on this study. I am now in group 2. And by the end of the year, who knows? (The eternal optimist, as always!)

Therefore, my advice for those who are still lucky enough not to have active disease: it’s time to act. The wait until the other shoe drops off attitude, which I have seen posted more than once on one of the MM listservs, infuriates me. And if your doctor scoffs at diet or exercise or supplements that have scientific backing (and curcumin is not the only one ), pay no attention. Look up the studies, print them out and take them to your doctor. That’s what I have done and still do. The best patient, or perhaps the most annoying one (depending on your point of view!) is a well-informed one.

Long ago, when sailing ships ruled the waves, a captain and his crew were in danger of being boarded by a pirate ship. As the crew became frantic, the captain bellowed to his First Mate, “Bring me my red shirt!” The First Mate quickly retrieved the captain’s red shirt, which the captain put on. He led the crew to battle the pirate boarding party and, although some casualties occurred among the crew, the pirates were repelled.

Later that day, the lookout screamed that there were two pirate vessels sending boarding parties. The crew cowered in fear, but the captain, calm as ever, bellowed, “Bring me my red shirt!” And once again the battle was on. The captain and his crew repelled both boarding parties; however, this time more casualties occurred.

Weary from the battles, the men sat around on deck that night recounting the day’s occurrences, when an ensign looked up at the captain and asked, “Sir, why did you call for your red shirt before the battle?” The captain calmly explained, “If I am wounded in battle, the red shirt does not show the wound, and thus you men will continue to fight unafraid…” The men sat in silence, marveling at the courage of such a man.

As dawn came the next morning, the lookout screamed that there were pirate ships on their way, ten of them, all with boarding parties. The men became silent and looked to the captain for his usual command. The captain, calm as ever, bellowed, “Bring me my brown pants!”

Here we go again. First it was mint leaves, now it’s olive leaves. Yesterday I was looking up something entirely different when I came across oleanolic acid, which is a triterpenoid (how’s that for a mouthful?) compound extracted from plant sources and food (even seedless raisins, I read). But it is also extracted from olive leaves (olea = olive). Olive leaves? Yes, I read that correctly: the leaves of Olea europaea, the common olive tree. I couldn’t stop reading, since I live in a country, indeed a region, famous for its delicious extra virgin olive oil (rightly so). Plus, my cousin is an extra virgin olive oil taster (yes, just like a sommelier, except she tastes and judges olive oil), and our wonderful extra virgin olive oil is given to us by a friend who owns an olive grove here in Tuscany.

So, just for the heck of it, I googled oleanolic acid and myeloma and, wouldn’t you know it?, there it was: a study on an olive leaf extract and MM cells, co-authored by Dr. Kenneth Anderson and published in "Molecular Cancer Therapeutics" in 2004. The full study can be read at: http://tinyurl.com/2okvod It is quite technical, but the conclusion is clear: a synthetic version of oleanolic acid, known as CDDO-Im, induced apoptosis in myeloma cells.

I called my husband, who laughed boy, those MM cells get killed by practically anything, don’t they? (Don’t we wish?!!!) But it (almost) seems to be true: any plant extract that I have looked up so far, and that has been tested in vitro against MM cells, appears to have an apoptotic effect on these malignant cells. Hmmm. Anyway, back to us and the oleanolic acid-MM study. In the Introduction, we can read that Chemoresistant MM cells have also been reported to inactivate anticancer drugs more efficiently than chemosensitive MM cells […]. In this regard, increases in the expression of glutathione (GSH) or the activity of GSH-related enzymes in MM cells has been associated with resistance to anticancer drugs […]. Novel treatment approaches that overcome such chemorefractory mechanisms may therefore be effective in the treatment of MM. CCDO-Im reduces the levels of GSH, which leads to the apoptosis of MM cells. The study continues: we analyzed the effects of the CDDO C-28 imidazolide ester (CDDO-Im) on MM cells. CDDO-Im is a potent inducer of apoptosis in MM cell lines and primary MM cells. Potent inducer of apoptosis in MM cells? What??? Hold on a sec, I’ll be right back. I am just going to pop over to ask my neighbour for some olive leaves from his gorgeous olive tree (see photo)! I could juice them! (Just kidding or am I? 😉 )

Other effects of oleanolic acid. It has anti-inflammatory, hepatoprotective and anti-hyperlipidemic properties, see this 1995 study: http://tinyurl.com/2aa7vm It has anti-HIV activity, according to this 1999 study: http://tinyurl.com/ypahk9, and wound-healing potential (http://tinyurl.com/ytczrr). A 1999 study (http://tinyurl.com/2rhdpu) tells us that it suppresses the abilities of various inflammatory cytokines, such as IFN-, interleukin-1, and tumor necrosis factor-, to induce de novo formation of the enzymes inducible nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse peritoneal macrophages, rat brain microglia, and human colon fibroblasts. CDDO will also protect rat brain hippocampal neurons from cell death induced by beta-amyloid. A 2003 study suggests that it be used in breast cancer therapy: http://tinyurl.com/338z7b. It also "can provide a cheap and accessible source of additive to conventional treatment of hypertension, complicated by stenocardia and cardiac failure" (http://tinyurl.com/yo2pvv). There seems to be no end to its potential. Oh, it also fights the bacteria that cause cavities and gum disease, so make sure you include oleanolic acid-containing raisins in your diet. Oleanolic acid can also be found in medicinal herbs such as ligustrum, forsythia, and swertia, which are used in China to treat hepatitis. I will stop here, but there would be much more.

Last but not least, according to the IMF website (http://tinyurl.com/3dlsmr), Johns-Hopkins and Dartmouth are testing oleanolic acid, which is now in the preclinical stage. In fact, this excellent bit of news is hot off the press, see the May 22 issue of the Myeloma Minute: http://tinyurl.com/22faba!

I have not posted about brands. As I have previously written, I do not want to make it seem as though I favour one brand over another. The fact is that I don’t know if there exists a best brand of curcumin. So why am I writing this post today? Simple. To help others in a situation similar to mine. If someone had given me any information about curcumin when I started taking it, I would have wasted less time looking up brand information, bioavailability issues, side effects, etc. These were the main reasons for creating this blog. Plus, I have privately received valuable information from other curcumin-takers, some of whom have been taking curcumin for longer than I have. That information should not go to waste.

So how do you choose what brand to take, and how do you decide if one curcumin-offering website is more reliable than another? These are legitimate questions. Please check my Curcumin Protocol post and page, and if you don’t find an answer there, remember that I will readily exchange information privately on this and other matters. Just write to me (if you know my e-mail) or leave me a note here, and I will get in touch with you. I may not be able to answer your questions, but I will try, at least! I should note that I am bilingual (Italian and English), plus I know enough French and Spanish to get by, so you can write to me in these four languages. Latin, too, if you wish. 😉

A slightly annoying note. Italian customs in Milan stopped a package containing resveratrol that my parents sent to me in May. They are just doing their job, but this means that I have now run out of the good resveratrol, and am taking what probably is not good enough for my resveratrol experiment. So, I fear that I will have to redo the experiment next fall. The latest word on the package is that customs has lost it. Sigh.

In spite of the customs mix-up and the horrible summer heat wave that is about to hit Florence (sigh), I have a few positive news items. My new kitten is adorable; I visit it every day. It is more interactive now, and looks up at me in wonder, as though it already knows how much I love it. Yesterday the little critter tried to show me how well it can clean itself but kept falling over in vain and clumsy attempts to clean its tiny hind paws. Too funny! Why it ? Well, we still can’t figure out if it’s a boy or a girl! I think it’s a girl, but could well be wrong. And the lonely kitten (see recent blog photo) has been adopted by a very pleasant young woman who passed a strict oral examination yesterday. 😉 And, last but not least, a close listserv friend, who had received what seemed to be very worrisome news about her MM, received some good news from a well-known MM specialist (hurray!). Life is good.

A blog friend recently sent me a list of substances that he found while doing research on another health-related topic. I am deeply obliged to him (thank you!) for telling me about another funny-sounding but deadly-to-cancer-cells compound: withanolide. Surprise surprise, in 2006 an MD Anderson team made the discovery that withanolides kill MM cells in vitro. The full study, published in Molecular Cancer Therapeutics, is available online: http://tinyurl.com/2eq3pc The study abstract begins: The plant Withania somnifera Dunal (Ashwagandha), also known as Indian ginseng, is widely used in the Ayurvedic system of medicine to treat tumors, inflammation, arthritis, asthma, and hypertension. Chemical investigation of the roots and leaves of this plant has yielded bioactive withanolides. Earlier studies showed that withanolides inhibit cyclooxygenase enzymes, lipid peroxidation, and proliferation of tumor cells. But even more importantly (for us MMers), in addition to suppressing the nasty COX-2 enzyme, these compounds blocked the activation of NF-kB in human myeloma (U266) cells. Yippee! And I would like to mention that a 2004 study shows that an extract of Withania somnifera inhibited angiogenesis: http://tinyurl.com/ypq58h

A 2003 University of Michigan study (http://tinyurl.com/yqmgxh) tells us that the roots of Withania somnifera are used as a dietary supplement around the world. Furthermore, from what I have read online, Withania somnifera is non-toxic, non-addictive and has no negative side effects (but I should say that I am still looking into this matter). Indeed, a recent study demonstrated that a purified standardized extract of ashwagandha protected the heart from the well-known cardiotoxic effects of doxorubicin: http://tinyurl.com/3yjcno And withanolides may also be effective against arthritis, see this June 2007 study: http://tinyurl.com/2vfw7r

The above-mentioned 2006 MD Anderson study concludes: Overall, our results suggest that the antiproliferative, proapoptotic, anti-invasive, antiosteoclastogenic, antiangiogenic, antimetastatic, radiosensitizing, antiarthritic, and cardioprotective effects assigned to withanolide may be mediated in part through the suppression of NF-kB and NF-kB-regulated gene products. Did I read anti-osteoclastogenic? Ahhhh, that rings a bell. This is a fascinating study, and not difficult to read, so I would urge all MMers to have a look at it.

Right now I am living in my fantasy world where MMers are killing off their nasty MM cells by taking a mixture of all these non toxic compounds. No horrible side effects, no pain. Some day, some day. Okay, out of my fantasy world and off to visit my kitten next-door now. Expect some photos over the weekend! 😉

I have been busy today and haven’t been able to do any research. So I am posting another kitten photo, taken this morning in my neighbours’ yard. 😉 Two of the kittens were adopted yesterday by a loving couple, so I am relieved. The third sibling was left behind, though, and appears to be very sad, even though it is still with its mother. Doesn’t this photo just tug at your heart strings? Poor little dear.

The most recent name suggestions from my family and listserv/blog friends for our three-week-old kitten are: Pammy, Petunia, Paloma, Pillola (which means “pill” in Italian) for a female; Pedro, Picasso, Paco, Philo, Pascal, Pasquale, Palmiro for a male. The name contest is still open!

This morning I read an interesting article titled “Forget fluoride – try turmeric.” In an attempt to stop the water supply in Onehunga, an Auckland suburb, from being flooded with fluoride, a New Zealand biochemist is trying to promote the idea that it is much safer to brush our teeth with turmeric. Since curcumin, turmeric’s active ingredient, has well-known antibacterial and anti-inflammatory properties, he is undoubtedly right! See: http://tinyurl.com/28cf85 Hmmm, but wouldn’t our teeth be stained yellow? I may do a test, just to see what happens…

No, this is not one of my humour posts. This is quite serious. 🙂

Gossypin is an antioxidant, anti-inflammatory flavone extracted from Hibiscus vitifolius, also known as tropical rose mallow, a perennial shrub. In 1978, this flavone (see: http://tinyurl.com/2gdp5l) was found to be effective against arthritis. It was compared to the standard nonsteroid anti-inflammatory agent phenylbutazone against various experimental models of inflammation and increased vascular permeability. The researchers found that gossypin was not as strong as phenylbutazone, but also not as toxic. And, while I am on the subject of pain relief, a 1997 study (http://tinyurl.com/2t37nz) concluded that gossypin could be used as a substitute for morphine, as it is well tolerated and is not habit-forming. Gossypin also has neuroprotective properties, see this 2004 study on rat cortical cells: http://tinyurl.com/yvwmws

But I saved the best news (for us MMers) for last. A 2003 study (http://tinyurl.com/ytdkxj) demonstrated gossypin’s antioxidant, antitumour and anti-carcinogenic properties. Gossypin reduced the tumour size in what were called solid tumor harboring animals, increasing their life span. And, even more significantly, the June 2007 issue of Blood features a study (http://tinyurl.com/2x4p5e) by an MD Anderson team, including Prof. Bharat Aggarwal, showing that gossypin inhibits the infamous NF-kB, suppresses the proliferation of COX-2, and enhances apoptosis of tumour cells. The abstract concludes that gossypin inhibits the NF-kB activation pathway, which may explain its role in the suppression of inflammation, carcinogenesis, and angiogenesis. Gossypin also blocks osteoclastogenesis. Excellent news.

Another non-toxic substance gets added to my to-be-watched-carefully list. 😉