Coconut milk and myeloma

An MMA list member (thank you!) recently posted the link to a Mayo news release on a compound in coconut milk called kinetin riboside that prevents the growth of myeloma cells. It actually kills them in large numbers: http://tinyurl.com/4sj3yy.

Large numbers, huh?! Why, that’s jolly spiffing! (I love that expression, must be my British heritage…).

 

The full Mayo study (http://tinyurl.com/5qfqyf) is available for free online. I haven’t had the time to give it more than a cursory glance, but I read enough to add kinetin riboside to my “to-be-monitored” list.

 

Interestingly, when I first began taking curcumin, I mixed curcumin powder with warm, almost hot, coconut milk, following a suggestion I received from Steve of the Grouppe Kurosawa. At that time, who would have thought that I might also have been ingesting a certain amount of this myeloma-killing compound?

 

And that brings us to the question: how much coconut milk would we have to swallow in order to start killing off our myeloma cells? Well, the answer is probably quite a lot because, as the Mayo study tells us, even though kinetin riboside is present in the human food chain, it occurs at low concentrations. And the Mayo news release tells us that it is present in minute quantities in coconut milk. Still…

 

I have to do more research…

 

Well, this is another promising development in the quest for a non-toxic but effective treatment for myeloma and possibly other types of cancer.

My goal in life.

Myeloma break

In the past few days, I have started wondering why I haven’t been feeling more eager to resume my almost daily routine of research into alternative treatments for myeloma, etc.
 
It didn’t take long to find an answer.
 
While we were in Northumberland, you see, I sort of turned into a “normal” person, someone who did not have a lethal form of cancer…even though my myeloma is inactive right now (as I write these words, I am knocking on wood and also, as Italians do, touching iron!). As far as I know…
 
For ten days I forgot that anything was wrong with me. I didn’t think about it even when I swallowed my curcumin. That gesture became part of the nightly routine: watch a BBC program, swallow my pills, read a book, go to bed.
 
I woke up every morning raring to go, regardless of the weather. We were well equipped for rainy, windy and cold weather, so nothing stopped us from setting off on our daily hikes. The day we went over the border into Scotland to visit the St. Abb’s Head National Nature Reserve (see photo; we were on top of a cliff there), we walked for about three hours up and down and across steep muddy hills and seaside cliffs. This was after we had been on another long hike earlier that day. I never thought I would have the energy to do anything like that.
 
But by then I had become an enthusiastic and (almost!) indefatigable walker.
 
Now, I don’t mean to imply that I am going to start trekking around the world and abandon my research or my blog….oh no, no, no, not at all. Research is a big part of my life now. And so is my blog and so are all of you.

I just need to ease back into my regular routine slowly.

A part of me is still holding on to that wonderful feeling of being “normal.”

Of not having cancer.

New hedgehog inhibitor: zerumbone

I think hedgehogs are among the most adorable creatures in the world. Under certain circumstances, though, the word “hedgehog” does not have a positive connotation, as we will see in this post. I refer specifically to the hedgehog signalling pathway, or Hh.
 
If you need to refresh your memory re. Hh, please have a look at my page on cyclopamine. Just quickly, though, as we can read in the abstract, this signaling pathway causes the formation and progression of a variety of tumors. And, in the full study: Besides its crucial roles in development, aberrant Hh/GLI signaling in adult tissues has recently been implicated in cancer formation and development, in the skin, brain, prostate, upper gastrointestinal tract, pancreas and lung.
 
Is the hedgehog pathway signalling also involved with myeloma? You betcha! Just take a quick look at this study (http://tinyurl.com/3zhw9h), which shows that the subset of MM cells that manifests Hh pathway activity is markedly concentrated within the tumor stem cell compartment. Hh and myeloma stem cells are best friends, simply put. But when the researchers used cyclopamine to block Hh, the clonal expansion of the myeloma stem cells was significantly affected. The myeloma stem cells, in other words, were not able to renew themselves. Groovy!
 
I am writing about this topic today because a Beating-Myeloma list member (thank you!) sent me a note about a recent study on zerumbone, a cytotoxic substance extracted from Zingiber zerumbet Smith, a sort of wild ginger. Sherlock sent me the full study (abstract: http://tinyurl.com/54xpp5).
 
Once again we come across our friend cyclopamine, the hedgehog antagonist that specifically inhibits Smo, an acronym that stands for Smoothened, a transmembrane protein necessary for the activation of hedgehog target genes. Smo mutations can disrupt the hedgehog pathway and lead to cancer. Obviously, not good!

At any rate, the researchers found that, like cyclopamine, zerumbone, the substance I am interested in right now, antagonizes Hh. One big difference, though. Cyclopamine, as I mentioned, targets Smo, an earlier stage of Hh, whereas zerumbone (and a few of the other compounds examined in this study) affects the final stage of Hh, which is called GLI1 (the acronym stands for “glioma-associated oncogene homolog 1,” aren’t you glad you know that? ).

The researchers tested 94 compounds from our natural product library, including terpenoids, flavonoids, phenylpropanoids, their glycosides and bisindole alkaloids […] and identified two sesquiterpenes and four bisindole alkaloids as inhibitors of GLI-mediated transcription. So they found six compounds that will inhibit GLI1, including zerumbone.

They also tested another 192 tropical plant extracts (extraordinary, no?), and those that were cytotoxic were again screened at lower concentrations. This part of the text, in fact MOST of the text, was very difficult for me to follow, so I had to skip some parts that were beyond my comprehension. A lot of it had to do with the procedures used in the screening, which we don’t really need to know (if anyone wants to read this very technical part, though, I would be happy to forward the study privately; just leave me a comment here).
 
The expression of the anti-apoptotic Bcl-2 protein is also involved with hedgehog. But the level of this protein was reduced by some of the compounds under scrutiny. This proves that hedgehog inhibitors also reduce the expression of the antiapoptotic protein Bcl2. This result also supports the reported relation between Hh antagonists and inhibition of Bcl2 expression.
 
Zerumbone is one of the compounds that suppresses the expression of the antiapoptotic protein Bcl2 and up-regulates the expression of the proapoptotic protein Bax; this results in an increase in the Bax/Bcl2 ratio. […] Our findings suggest that the suppression of Bcl2 expression might be due to the inhibition of GLI-mediated transcription. Inhibit the hedgehog signalling pathway, in other words, and Bcl-2, one of the bad guys, is also affected. Two birds with one stone. Sounds good to me!
 
The researchers examined a human pancreatic cancer cell line (PANC1), which expresses numerous Hh/GLI signaling pathway components. They found that the compounds inhibit the expression of these components at the transcriptional level. Take my word for it, this is important. And since, as I have mentioned, other natural extracts were tested in addition to zerumbone, I have a lot of work ahead of me.

One last bit of intriguing news, though: zerumbone also inhibits the Epstein-Barr virus…see: http://tinyurl.com/4lbh92 Well, it’s getting late, and I must get off this computer.

I can tell that this is going to be a long hedgehog weekend! 

Broccoli for immunity

I have been very busy (in a good sense!) these last couple of days, and today is no exception, which means I don’t have time to do any research or answer any e-mails, sooooorry! 
 
I did, however, want to post the link to a recent Science Daily article (http://tinyurl.com/29ohml) on broccoli, which contains a fantastic chemical (about which I have already written, see my Page on broccoli) called sulforaphane. Sulforaphane “switches on a set of antioxidant genes and enzymes in specific immune cells, which then combat the injurious effects of molecules known as free radicals that can damage cells and lead to disease.” This means that by eating broccoli we may be able to slow down what one of the UCLA researchers called “the age-related decline in immune function.”
 
Read this: “In particular, the scientists discovered that dendritic cells, which introduce infectious agents and foreign substances to the immune system, were particularly effective in restoring immune function in aged animals when treated with sulforaphane.” Indeed, when sulforaphane was administered to old mice, their immune systems became as efficient as those of young mice. Well, well.
 
Hmmm, it just so happens that I will be making (and freezing for future use) a bit of broccoli pesto today. And here is my easy-peasy recipe:
  1. Wash and cut some broccoli florets, as many as you want, into half or quarters, depending on size. Let them sit for 5 minutes or so before cooking so that the cancer-preventive compounds have time to form (see: http://tinyurl.com/9tjdw). Steam them for no more than 5 minutes. Overcooked broccoli has about the same nutritional content of cardboard, so watch out.
  2. Crush or mince some fresh garlic, again as much as you want, but don’t go overboard!, and, as you did for the broccoli, set it aside for 5-10 minutes (see why here: http://tinyurl.com/2yzh9g). If you don’t care for the strong taste of fresh garlic, prepare the fresh garlic as above and slightly steam it with the broccoli. A solution for any problem…!
  3. Blend the broccoli and garlic…in a blender together with a bit of extra virgin olive oil, salt and pepper (omit the latter if you are on eight grams of curcumin WITH bioperine, which is a black pepper extract, so we don’t want to consume too much extra pepper on a daily basis). If the mixture is too stiff, just add some water from the pot where you steamed the broccoli (aha!).
  4. If you want, you can add a bit of hot red pepper for the capsaicin (a myeloma-cell-killer in vitro!). I may also try adding a dash of turmeric today. Hmmm.
That’s it for now. I have to get back to work! Take care, everyone!

Fear

As I have mentioned on previous occasions, I subscribe to the Cancer Compass newsletter where I frequently come across items of interest. I read one such item yesterday, titled “A patient’s perception of peril can cloud treatment decisions.” It discusses the feelings surrounding a cancer diagnosis, feelings such as fear that can sometimes lead us to make mistakes.

An excerpt (you can read the full text here: http://tinyurl.com/344rsl): often, a patient’s perception of peril – whether before a screening test or upon a definitive diagnosis – exceeds the genuine risk and can cloud treatment decisions. The fear is a reflection, in many respects, of what science has wrought in recent decades: More cancers than ever are being diagnosed, and they’re being found earlier and earlier. Tumors that would have gone unnoticed and untreated in an earlier era are now identified and addressed, even when the benefits aren’t fully clear.

"We’ve exaggerated the efficacy of our treatment and prevention at the same time we’ve spread fear of cancer," said Dr. Robert A. Aronowitz of the University of Pennsylvania, who has studied the history of cancer extensively. "And it’s led to a lot of individual and policy level mistakes.”

The benefits aren’t fully clear?…We’ve exaggerated the efficacy of our treatment and prevention? Whoa!!!

This reminded me of when my former haematologist was pushing me to begin Velcade in the fall of 2005, and had introduced the possibility of chemotherapy even earlier that year. He told me that we shouldn’t wait until I began having symptoms (bone lesions and whatnot). Well, today I ask myself: where would I be now if I had been overcome by fear and followed his advice? I don’t mean to sound judgmental of those who choose conventional treatments, oh no, quite the opposite!…what I mean is that sometimes, or even frequently, as Dr. Aronowitz admits, our doctors tend to scare us…perhaps (!) unnecessarily…into making hasty decisions. Remember the case of Michael Gearin-Tosh? (see the link here on the right, under "MM blogs/sites.")

Cancer is still seen by many as a death sentence, so it’s natural to be scared. I have been scared, too. And, heck, I still have some fear on an occasional basis, in spite of my incurable () optimism. I have already written a bit about my reaction to finding out that I had benign MGUS (I burst into tears in my car) and, many years later, myeloma (a few more tears, soon replaced by determination). But, luckily for me, I was, still am, in an early stage, and had time to think and do research. I sought other medical opinions (Dr. Robert Kyle was one of the myeloma specialists who confirmed I was right to wait, by the way). If you are diagnosed with MGUS, SMM or MM (at any stage, but an early stage in particular), I urge you to read Michael Gearin-Tosh’s book, "Living Proof." He writes, if you are diagnosed with cancer, you need time to think. So true. Thinking is not enough, though. There are other things you can do. As follows.
 
We (patients) can ease the fear of cancer, according to the Cancer Compass article, by being informed. Find out everything that you possibly can about your type of cancer. A recent study found that men’s concerns about prostate cancer eased – once they received information via a sophisticated Internet program. Bingo! 
 
Information, say cancer specialists, “is not only power. It can also forge hope. That’s exactly what happened when parents whose children were gravely ill with cancer received a more detailed description of how the disease might progress. The families getting the most information reported the greatest degree of hope, even in the face of a grim prognosis. And, even though such matters are not mentioned in this article (quelle surprise!), don’t forget to research, and speak to your healthcare provider about, diet and supplements.
 
When I was first diagnosed with myeloma, some of Stefano’s relatives became concerned that I was doing so much research online. "It is better for her not to know," they whispered to him. Well, today I feel vindicated: it is better to KNOW.
 
The Cancer Compass article mentions something that I have experienced, too. That I still experience, in fact! Whenever I get an unfamiliar or odd ache or pain, the first thing that pops into my mind is “oh bother, is this the myeloma, is this a bone lesion?” (Okay, so I use much stronger words than "bother"! ). Apparently, that’s a normal reaction (phew). So what do I do about it? Well, I simply tell myself not to be silly, shrug my shoulders and forget about it. The pain goes away.

I’d like to end today’s post with the following excerpt from "Living Proof": Even if you find it difficult to go so far in your own thinking, active involvement in your therapy may lead to your consciousness and subconscious to trigger complex biological creativities, a presence in you of ‘decisions of endless creation’ that may help to fight a terrible disease.

Thank you, Michael.

Gossypol analogue

Remember my post on gossypin? Okay, well, today’s post has nothing at all to do with gossypin. (Hehe, sorry, couldn’t resist. ) But really, the word "gossypin" sounds like the substance I am about to discuss: "gossypol," which I thought was a derivative of gossypin, at first. But no, gossypin is a flavone extracted from the tropical rose mallow plant, whereas today’s protagonist, gossypol, is a polyphenol derived from the cotton plant. So, different compounds.
 
Gossypol, I read online, has been used for centuries against malaria and as a male contraceptive in China. The cotton plant produces gossypol to protect itself from the damage caused by pesky insects. It’s a toxin that inhibits the reproduction of insects and also of humans (mammals in general). Anyway, what I found interesting is that gossypol is now being studied for its anticancer properties. An all-too-familiar story!
 
The new edition of “Blood” (March 15 2008) has a study on a gossypol semi-synthetic analogue called "apogossypol" that apparently is more effective than gossypol against Bcl-2, an anti-apoptotic gene that almost certainly has a lot to do with the chemoresistance of myeloma cells. Brief aside: you can do a search here for Bcl-2, just scroll to the bottom of my Blogroll until you reach a "search" box; see in particular my August 27 2007 post titled “Survivin MM with curcumin.”
 
Sherlock (grazie!) sent me the full study; you can view the abstract here: http://tinyurl.com/ytsvdh The study begins with a look at the above-mentioned Bcl-2, which is overexpressed in many cancers and leukaemias and protects tumours and leukemic cells from kicking the bucket when exposed to chemotherapy, hormonal treatment or radiation. Bcl-2 has thus become a target for cancer treatment, especially where B-cell malignancies are concerned (non-Hodgkin lymphoma and CLL, in particular).
 
The study tells us that another gossypol analogue, AT-101, is being tested right now in Phase 1 and 2 clinical trials on patients with solid tumours, lymphomas and leukaemia. I checked to see what kind of clinical trials were testing gossypol, and there are twelve trials for different kinds of cancer ranging from brain to prostate cancer. And, of course, B-malignancies. The main problem of AT-101, though, appears to be the GI toxicity caused by its bothersome aldehydes; we don’t need to know what these are exactly, just that their removal eliminates any GI problems. The "Blood" study researchers did just that: they removed the aldehydes, thus creating apogossypol, which shows “superior blood concentrations over time […] compared with gossypol, due to slower clearance of the compound.”
 
Toxicity: the researchers tested the toxicity of gossypol and its analogue on normal female Balb/c mice (okay, I confess that I still shudder with horror when I think of all the suffering lab animals around the world…and to tell the truth, if someone told me, “it’s either you or that mouse,” it would be a tough choice for me to make, as silly as that probably sounds. If the choice were between me or a cat, well, you can imagine what my answer would be…now why can’t experiments be done on those maddening tiger mosquitoes??? ).
 
Back to the study. Well, apogossypol turned out to be less toxic than its parent compound. If you want to read more details, I will be happy to forward the study to you. Other results: unlike apogossypol, gossypol was toxic to the liver, caused GI problems and made the mice lose weight. Neither substance caused any kidney toxicity or heart trouble. Ok, I’ve read enough about the poor dear lab mice. Basta!
 
In vitro findings (phew, much better: I don’t have as much sympathy for cancer cells…). The researchers used “cultured B-cell lymphoma and CLL leukemia cells.” In both cell cultures, apogossypol was more lethal than gossypol.
 
The gist of the study: “The preclinical data presented here show superior efficacy and markedly reduced toxicity of apogossypol compared with gossypol, and thus indicate that further development of apogossypol for B-cell malignancies is warranted.” Well, interesting study. Another piece of the puzzle, perhaps. Only time will tell…

The history of multiple myeloma

As I was looking through the new edition of “Blood” yesterday, I came across an interesting historical overview of multiple myeloma by Dr. Robert Kyle (with whom I have spoken by phone and been in touch with occasionally since 2005: an extremely nice, kind, reassuring doctor) and Dr. Vincent Rajkumar, Mayo Clinic in Rochester.
 
The full text is available online: http://tinyurl.com/2r7gw3, so I won’t go into any detail. I would like to mention, though, that I am very glad that myeloma is no longer being treated with leeches…
 
Just a few words. The “first well-documented case” of myeloma dates to 1844: a woman, 39 years old. The best known case is that of a 45-year-old man (again in 1844) who was given quinine and steel (?). And a sample of his urine was sent to….Dr. Henry Bence Jones. Ring any bells?

Interesting read. However, I hope it won’t take another 50 years for this history of multiple myeloma to have a chapter on curcumin and other natural, non toxic treatments. Oh, and while we are at it, how about a chapter on the non toxic cures: cyclopamine or DMAPT, the myeloma stem cell terminators?

An impossible dream? Perhaps…

Perhaps not.

Mayo EGCG study

Thanks to Don (see the link to his blog, Myeloma Hope, on the right), Sherlock and I found out about a 2005 Mayo Clinic study on EGCG (green tea extract, see my permanent page for more information). Sherlock looked it up and sent me the full study (abstract, 2006: http://tinyurl.com/29dyp5), which I read this morning. I almost cried with joy.

In a nutshell, after reading a Mayo in vitro report on EGCG’s annihilation of human CLL (chronic lymphocytic leukemia) cells, several Mayo (and probably non Mayo!) patients with CLL began taking this extract on their own. The researchers report that they became “aware of four patients with low-grade B malignancies,” who “appeared to have an objective clinical response.” Three of them achieved partial response (PR). I would like to note that their markers had been worsening before they began taking EGCG: “Several patients presented here had documented steady clinical, laboratory, and/or radiographic evidence of progression immediately prior to initiation of over-the-counter green tea products and then developed objective responses shortly after self-initiating this therapy.”

A "quick" parenthesis. During the discussion period at the NF-kB-curcumin-cancer conference on Saturday (see previous post), I was sitting up front with the other panel members, facing the audience. Next to me was a very nice doctor, I think a urologist (but wouldn’t bet my life on that). Well, in response to a question about why the Tuscan Regional Government doesn’t promote the use of curcumin, since it works for so many patients, scientific studies support its use in cancer treatment, AND it’s cheaper than many drugs, the good doctor answered, more or less, that science needs time, that anecdotal evidence is not scientific proof, that we have to wait until clinical trials are set up, the results published, blablabla. (I wish this cautious man had been on the Avastin committee, by the way!)
 
I waited until he had finished, took the microphone, and replied “you are right. Science needs time. But we are patients, cancer patients, and we don’t have that kind of time. If, for instance, I had waited for the results of the MD Anderson curcumin-myeloma clinical trial to be published, I don’t know how I would be doing right now. The first results from the trial were presented in December 2007, that is, almost two years after I began taking curcumin.” I forget what I added, but the tape should remind me (and perhaps slightly amend what I just wrote). At any rate, as I remember (!), he agreed that I was right.

Obviously, I am NOT suggesting that we (cancer patients) go out and try just ANYTHING. That would be absurd and dangerous. Beware of websites that tell you that they can cure your cancer! Avoid those like the plague.

But some substances, such as curcumin extracted from turmeric and EGCG from green tea, have been used for centuries to treat all sorts of ailments, as we know. So I am talking about "ancient" non toxic substances that have in recent years been studied in vitro and in vivo and have scientifically-proven anticancer and chemopreventive effects. These results are not anecdotal anymore. I am not the only myeloma patient to have had success with curcumin (sure, a few haven’t achieved similar results, but that is why we, patients, have to TRY it to see if it works in our particular situation).

My stance is, therefore: what’s the harm in trying a scientifically-proven, non toxic substance for eight weeks to see if your markers improve? If they do, then why not continue taking it? Unless, of course!, you have some health issue such as obstructed bile ducts in the case of curcumin (see my Warnings page).

Okay, so the parenthesis wasn’t "quick" at all!  Let’s have a close look at the Mayo EGCG study. The full study.
 
According to the Mayo researchers, “EGCG also reduced levels of the protein Mcl-1, an anti-apoptotic protein of known importance in CLL B-cell resistance to apoptosis,” at very very low doses. As usual, I looked up this protein in reference to multiple myeloma, and DUH!, wouldn’t you know it!, the blasted thing turns out to be “essential” for the survival of human myeloma cells in vitro, see abstract: http://tinyurl.com/yuhlku. Essential! 
 
The study provides a detailed description of four CLL cases. Patient number 1 is a 58-year-old woman diagnosed with the “small lymphocytic lymphoma (SLL) variant of CLL/SLL,” whose BMB in 2003, 20 months after diagnosis, showed a “20–25% marrow involvement by CLL/SLL B-cells.” She began taking an OTC (over the counter) green tea supplement containing 315 mg of tea polyphenols. Twice a day. Within a year, “she demonstrated a steady clinical and radiographic decline in her lymphadenopathy with >50% reduction in bilateral axillary nodes and near normalization in the size of all other areas of adenopathy. The patient’s reduction in lymph node size met the NCI criteria for a partial response (PR).” She is doing well (this report was written at 44 months after her diagnosis) and “has not required conventional therapy.”
 
Patient number 2, a woman, 55 years old, was diagnosed with stage IV disease, asymptomatic. She began drinking a cup of green tea every day ( = two tea bags). Result, 20 months after her initial diagnosis: “>50% decrease in the sum of the products of the six largest lymph node areas consistent with a PR according to the International Working Group criteria for non-Hodgkins lymphoma.”
 
Patient 3, woman, 50 years old. Five years after being diagnosed with Rai stage 0 CLL (see here for info on CLL staging: http://tinyurl.com/yo2u8m), her absolute lymphocyte count (or ALC) increased, and she developed night sweats and fatigue (that sounds so familiar to me: back in the pre-curcumin era, in 2005, I had both of those symptoms). After reading the Mayo report, she began using a green tea patch, “labeled as containing 300 mg polyphenols,” and drinking three green tea packets a day (300 mg polyphenols per packet). Just one month later her markers had improved. At the time of the report, 77 months after her diagnosis, even though she discontinued the patch and was drinking only one packet of green tea per day, she was classified as stable. No conventional therapy.
 
The last patient mentioned in the Mayo report is a 60-year-old woman diagnosed with Rai stage 0 CLL in 1995. In 2004 her WBC (white blood count) and ALC increased. This concerned her, so (again, after reading the Mayo in vitro report) she began drinking eight cups of green tea per day. After just one week (ONE WEEK!) her markers had improved. She continued drinking green tea, and her ALC decreased by 50%. 120 months from diagnosis, she “is still asymptomatic from her CLL.”
 
The discussion part of the study tells us that “In total, our report on these patients with low grade B-cell malignancies adds to the growing evidence that food products that contain polyphenols have anti-tumor activity. In fact, the polyphenol containing agents have not only been shown to have anti-tumor activity but have been linked to chemoprevention of human tumors. A number of epidemiologic studies have linked consumption of green tea to a decreased risk of cancer. A wide range of animal models has also supported green tea’s ability to prevent tumorigenesis. Multiple mechanisms have been proposed as the explanation of the effect of green tea, including anti-angiogenic properties, DNA damage, and inhibition of telomerase. More recent studies of EGCG suggest this agent may affect folate metabolism, suppress transcription factors leading to cell-cycle arrest, and induce oxidative stress through generation of ROS. In vitro studies have also shown EGCG decreases levels of anti-apoptotic proteins at drug levels which are achieved in the serum of tea drinkers in vivo.” Sorry for this tremendously long quote, but there was really no way to summarize or shorten it.

The Mayo report is about CLL patients, of course, but let’s not forget that EGCG has been shown to work against myeloma cells, too. And in fact I am in touch with quite a number of MGUS and SMM folks who take this supplement or drink green tea. Successfully. So now I am more curious than ever to find out how Sherlock and I will do on one gram of EGCG combined with our eight grams of curcumin.

Oh, another important note: the study points out that EGCG should be taken on an empty stomach: “The plasma concentration of free EGCG could be increased five-fold when taken in fasting conditions rather than with food.” If you choose to drink green tea (té verde, in Italian) rather than take an EGCG supplement, by the way, well, in this photo Priscilla, my two-year-old cat, demonstrates how to drink it properly (raise your cup to your mouth…just like this). Sorry, couldn’t resist, she is TOO cute.

The Mayo researchers’ final words, which echo the above-mentioned Italian conference doctor’s thoughts: “These anecdotes cannot determine the effectiveness of tea polyphenols, and highlight the need for clinical trials to define the optimal dosing, schedule, toxicities, and clinical benefits before widespread use can be recommended.” The Mayo EGCG clinical trial is currently recruiting CLL patients, by the way: http://tinyurl.com/2p5l8q.
 
Well, in my opinion, the Mayo report shows that sometimes we patients just have to jump the gun…proceeding, of course, with well-informed, scientifically-based caution, as always.

Curcumin-cancer conference in Calenzano

Yesterday I presented my experience with curcumin and my blog in front of a crowd of (mainly) doctors and oncologists. You know how you are a nervous wreck and have scary nightmares the day/night before you have a university exam or a job interview? Then you will understand what happened to me on Friday night. I tossed and turned and barely slept a wink. One of my nightmares was all about how I was delayed (through no fault of my own) and totally missed the conference, arriving there the day AFTER. Typical, huh?

Ironically, my nightmare almost came true. We arrived late, a half hour late. I am never ever (never!) late for anything, so this was very trying for me. What happened was that Sherlock, Stefano and I got totally lost in the maze of roads outside of Florence. It should have taken us about 20 minutes to get there. It took an hour plus. Stefano’s GPS system couldn’t locate the castle of Calenzano, so it kept sending us back and forth, hither and thither. And when we paused to ask the locals where the castle of Calenzano was, we got all sorts of conflicting directions. One woman told us to turn left and go back toward Florence, a couple of guys told us to take a right, then the second left, then…you get the picture. A mess!  However, we finally made it to the castle (lovely Medieval castle, by the way, see photos) where we ran into a group of equally frazzled doctors. They were late, too! As a result, the conference began late, so this all ended up being amusing.

The conference was enthralling. The speakers presented their research in a very clear and concise manner. First-rate. Their slides were brilliant visual aids. Even my cousin, who reads my blog but otherwise has little knowledge of transcription factors and whatnot, reported that the speeches were easy to follow. Thanks to Sherlock, I taped the entire event and hope that at least some of it of it ends up being comprehensible. The audio in the auditorium (which was full, I would like to add) wasn’t the best, even though that sounds a bit…odd (audio-auditorium…). 

Mine was the last speech. Since up till then all the talk had been about prostate cancer, transcription factors, genomes, chemoprevention and whatnot, I decided on the spur of the moment to start with something silly. So my speech began, more or less, “Today I am going to present my case. First, I would like to clarify that I do not have prostate cancer (laughter around the room) but multiple myeloma…” After describing multiple myeloma and my medical background in a few words, I then went on to talk about how I discovered curcumin and why I created my blog. According to Stefano, my aunt and cousin (who were there, too), I got the loudest and longest applause. I was so relieved that I had gotten through my speech without fumbling or falling over the microphone cord, though, that I didn’t even hear the clapping!

After the discussion session, I was approached by a few members of the audience and then by reporters from two Florentine newspapers. The articles were published today. Unfortunately, I am identified as having an "incurable pathology," and the words "multiple myeloma" are not even mentioned.

I met a couple of German researchers, one works in Genoa at the National Institute for Cancer Research, the other in the Department of Chemistry and Biochemistry of the University of Munich. They are studying curcumin and its effect on prostate and breast cancers, and are preparing a double-blind, placebo-controlled clinical trial to test curcumin on 100 or more cancer patients. Of course, I told them that if they needed a myeloma patient, I’d be on the next train to Genoa! This isn’t going to happen tomorrow, of course. Anyway, very interesting.

Well, I will probably have more to say on this matter once I have read Dr. Benelli’s book on NF-kappaB and listened to the taped conference. For now, this is it.

Need an excuse to drink coffee?

Thanks to Sherlock, who sent me the full study that I will be discussing today, and to a Grouppe Kurosawa mailing, I found out something that I had not previously known about coffee. As it did for yours truly, the following should put a smile on the faces of coffee drinkers. This was meant to be a simple brief discussion of a study on caffeine, but it turned into a huge time-consuming bit of research. One thing led to another…I did my best not to go overboard!
 
An Italian study (see abstract: http://tinyurl.com/3862f5) published in May 2007 in “Molecular Pharmacology” states that caffeine inhibits VEGF and IL-8 (interleukin-8) in human colon cancer cells. Specifically, it inhibits HIF-1 alpha, or “hypoxia-inducible factor alpha.” Let’s take a closer look at HIF-1 alpha before proceeding.

I read that solid tumours are unable to grow beyond a certain size because of hypoxia, which means "insufficient oxygen." What happens is that, as tumours grow, they need more and more nutrients and oxygen. At a certain point, though. the tumour microenvironment just can’t deal with this constant demand (if I got that right…) and becomes hypoxic. Under hypoxic conditions (less than 6% oxygen, I read), HIF-1 alpha, a transcription factor, becomes activated, and it in turn activates genes, dozens of them!, that keep tumours alive and well, via angiogenesis, glucose transport and whatnot. So tumour progression goes hand in hand with the increased activity of HIF-1 alpha.

Is this bothersome transcription factor present in myeloma, I wondered for just a split second? I really didn’t need to do a search to answer that question.  But I did do a search, and, quelle surprise!, it turns out that HIF-1 alpha is involved in myeloma angiogenesis as well. See this Italian study: http://tinyurl.com/36eywf. And see also this very colourful PDF presentation prepared by an Italian team for the 10th International Myeloma Workshop (Sydney, 2005): http://tinyurl.com/ytwej8 It also shows the involvement of HIF-1 alpha in myeloma angiogenesis.

Back to the Italian study on caffeine (see abstract): “Pretreatment of cells with caffeine significantly reduces adenosine-induced VEGF promoter activity and VEGF and IL-8 expression.” (Wait…adenosine? Uffa, another thing to look up…) Here we go: simply put, adenosine is a natural chemical, a neurotransmitter, released by brain cells to make us sleepy. The more we stay awake, the more adenosine gets released. But I should point out that adenosine is present also in all cells of the body, and, aha!, has the function of protecting cells from damage under conditions of hypoxia.  And it protects solid tumours from the attacks of NK cells and T-lymphocytes, as can be seen in this abstract (“International Journal of Oncology,” March 2008): http://tinyurl.com/yu7o72. It seems to be involved in a lot of mischief! Well, ok, not all the time!, for instance it mediates the damage caused by strokes…

Enough. You can read more about the importance of adenosine on the Grouppe Kurosawa public blog (February 29 post): http://tinyurl.com/23fbgo. The main thing we need to know is that, when adenosine is released, HIF-1 alpha and VEGF, the very best friends of cancer cells, are activated.

I started going through the Italian caffeine study with my usual (exaggerated!) attention to detail, then I decided that that didn’t make any sense. Do we really care that much about how this all works? Naaah. The important thing is the study’s clear message (well, to me, a morning coffee drinker, at least!): DRINK COFFEE! (yes, yes, YES…!).
 
Okay, just a few points (can’t help it, sorry! ):
  1. Hypoxic tumour cells are resistant to chemotherapy and radiotherapy. Eh!
  2. Hypoxia stimulates IL-8, which is involved with cancer progression (including myeloma progression, as we know from a previous post).
  3. HIF-1 “contributes to tumor progression and metastasis.”
This, according to the authors, “is the first report examining the in vitro effect of caffeine on hypoxic cancer cells.” Their “data suggest three potential chemopreventive targets for caffeine: 1) HIF; 2) VEGF and IL-8; and 3) cell migration.” They add: “our results indicate that, in tumor colon hypoxic cells, adenosine increases VEGF promoter activity via the HIF-1 pathway and that caffeine is able to block this effect.”
 
Now, while the cancer cells studied here were not myeloma ones, there is quite a bit of common ground, as we have seen (VEGF, IL-8 etc.). So I will be interested to read future studies on this topic. In the meantime, I will enjoy my usual morning homemade cappuccino with much more gusto!
 
Oh, I just can’t resist adding this lovely titbit at the end.  Guess what other substance inhibits HIF-1 alpha? Any ideas? Yes! CURCUMIN! (I always check…). See this abstract, published in “Oncology Reports” in 2006: http://tinyurl.com/2aooud It suggests that “curcumin may play pivotal roles in tumor suppression via the inhibition of HIF-1 alpha-mediated angiogenesis.” And a “Molecular Pharmacology” 2006 study (full text: http://tinyurl.com/27q93o) also suggests that curcumin inhibits tumour growth by targeting this transcription factor.
 
HAH! Now I have TWO good reasons to be happy today!