Mayo EGCG study

March 10, 2008 / / 34 Comments

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

March 9, 2008 / / 18 Comments

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.

Being thankful for things that…didn’t happen…

March 6, 2008 / / 1 Comment

The other day I was reading bits and pieces from “The uncollected Wodehouse” when I came across a gem that I thought I would write about today. P.G. Wodehouse, by the way, is best known for his Jeeves (the brainy butler) character. If you have never read the Jeeves and Wooster books and need a laugh, rush over to the library and borrow some. And if you have never seen the TV series, rent it immediately: the one with Stephen Fry magnificently portraying Jeeves and an equally magnificent Hugh Laurie (yes, Dr. House) playing the part of Bertie Wooster, the scatterbrained aristocrat. But this is neither here nor there.

Point is, I read a two-page story titled “The secret pleasures of Reginald.” This long (sorry!) excerpt (I took parts of it out, so as to shorten it, but you can read the entire story here: http://tinyurl.com/yw43js) illustrates Reggie’s “thankful…not” theory:

I found Reggie in the club one Saturday afternoon. He was reclining in a long chair, motionless, his eyes fixed glassily on the ceiling. He frowned a little when I spoke. "You don’t seem to be doing anything," I said.

"It’s not what I’m doing, it’s what I am not doing that matters."

It sounded like an epigram, but epigrams are so little associated with Reggie that I ventured to ask what he meant.

He sighed. "Ah well," he said. "I suppose the sooner I tell you, the sooner you’ll go. Do you know Bodfish?"

I shuddered. "Wilkinson Bodfish? I do."

"Have you ever spent a weekend at Bodfish’s place in the country?"

I shuddered again. "I have."

"Well, I’m not spending the weekend at Bodfish’s place in the country."

"I see you’re not. But — "

"You don’t understand. I do not mean that I am simply absent from Bodfish’s place in the country. I mean that I am deliberately not spending the weekend there. When you interrupted me just now, I was not strolling down to Bodfish’s garage, listening to his prattle about his new car." […]

I got his true meaning. "I see. You mean that you will be thanking your stars that you aren’t with Bodfish."

"That is it, put crudely. But I go further. I don’t indulge in a mere momentary self-congratulation, I do the thing thoroughly. If I were weekending at Bodfish’s, I should have arrived there just half an hour ago. I therefore selected that moment for beginning not to weekend with Bodfish. I settled myself in this chair and I did not have my back slapped at the station. A few minutes later I was not whirling along the country roads, trying to balance the car with my legs and an elbow. Time passed, and I was not shaking hands with Mrs. Bodfish. I have just had the most corking half-hour, and shortly – when you have remembered an appointment – I shall go on having it. What I am really looking forward to is the happy time after dinner. I shall pass it in not playing bridge with Bodfish, Mrs. Bodfish, and a neighbor. Sunday morning is the best part of the whole weekend, though. That is when I shall most enjoy myself. Do you know a man named Pringle? Next Saturday I am not going to stay with Pringle. I forget who is not to be my host the Saturday after that. I have so many engagements of this kind that I lose track of them."

"But, Reggie, this is genius. You have hit on the greatest idea of the age. You might extend this system of yours."

This is genius, indeed. We normally use the adjective “thankful” to express appreciation for a positive experience or whatnot. But how about being thankful for things that did NOT happen? In fact, I can think of a number of things for which I am thankful…not.

For instance, I am thankful that I did NOT accept a teaching position at a university in Canada many years ago, before I was awarded my Ph.D. I love Canada, loved living there, don’t get me wrong, but for some reason, when I was offered this job on a silver platter, something that I can best describe as a gut feeling induced me to decline. It was as though I KNEW that I had to leave for Italy that fall. Now, for someone in my position, i.e., a jobless Ph.D. candidate, it was a crazy thing to do (what was I thinking?!)–but I listened to my gut feeling and flew to Italy.

And I met Stefano. If I hadn’t turned down the teaching job, we wouldn’t be together today. Yes, there are indeed worse things than spending a weekend with Bodfish.

Heaven and hell…

March 5, 2008 / / 2 Comments

While walking down the street one day a U.S. senator is hit by a bus and dies. His soul arrives in heaven and is met by St. Peter at the entrance.

"Welcome to heaven," says St. Peter. "Before you settle in, it seems there is a problem. We seldom see a high official around these parts, you see, so we’re not sure what to do with you."

"No problem, just let me in," says the man.

"Well, I’d like to, but I have orders from higher up. What we’ll do is have you spend one day in hell and one in heaven. Then you can choose where to spend eternity."

"Really, I’ve made up my mind. I want to be in heaven," the senator protests.

"I’m sorry, but we have our rules."

And with that, St. Peter escorts him to the elevator and he goes down, down, down to hell. The doors open and he finds himself in the middle of a green golf course. In the distance is a clubhouse and standing in front of it are all his friends and other politicians who had worked with him.

Everyone is very happy and in evening dress. They run to greet him, shake his hand, and reminisce about the good times they had while getting rich at the expense of the people. They play a friendly game of golf and then dine on lobster, caviar and champagne.

Also present is the devil, who really is a very friendly guy who has a good time dancing and telling jokes. They are having such a good time that before he realizes it, it is time to go. Everyone gives him a hearty farewell and waves while the elevator rises…The elevator goes up, up, up and the door reopens on heaven where St. Peter is waiting for him.

"Now it’s time to visit heaven."

So, 24 hours pass with the senator joining a group of contented souls moving from cloud to cloud, playing the harp and singing. They have a good time and, before he realizes it, the 24 hours have gone by, and St. Peter returns.

"Well, then, you’ve spent a day in hell and another in heaven. Now choose your eternity."

The senator reflects for a minute, then he answers: "Well, I would never have said it before, I mean heaven has been delightful, but I think I would be better off in hell."

So St. Peter escorts him to the elevator and he goes down, down, down to hell. Now the doors of the elevator open and he’s in the middle of a barren land covered with waste and garbage. He sees all his friends, dressed in rags, picking up the trash and putting it in black bags as more trash falls from above.

The devil comes over to him and puts his arm around his shoulder. "I don’t understand," stammers the senator. "Yesterday I was here and there was a golf course and clubhouse, and we ate lobster and caviar, drank champagne, and danced and had a great time. Now there’s just a wasteland full of garbage and my friends look miserable. What happened?"

The devil looks at him, smiles and says, "Yesterday we were campaigning. Today you voted."

Avastin: a tale of appalling approval

March 4, 2008 / / 3 Comments

I love the idea of starving a tumour to death by cutting off its blood supply. That is what anti-angiogenic drugs are supposed to do. But first, what exactly is angiogenesis? I have mentioned this process here and there but don’t think I really have dealt with it in much depth. So yesterday and then today, after getting home from work, I looked it up.

From a previous post we know that tumours cannot grow beyond a certain size (the size of a sesame seed, I read!) because of a lack of oxygen and nutrients. But, unfortunately for us, tumours are very adaptable, so instead of kicking the bucket they start secreting a horde of growth factors (e.g., the infamous VEGF, or vascular endothelial growth factor) which induce angiogenesis, or blood vessel growth. The tumour is thus able to receive a constant supply of nutrients and can grow inside of us like a nasty weed. Without the process of angiogenesis, tumours wouldn’t be able to grow or spread.

In 2004, an anti-angiogenic drug called bevacizumab (trade name: Avastin) was approved by the FDA “for use in combination with standard chemotherapy in the treatment of metastatic colon cancer and most forms of metastatic non-small cell lung cancer. In 2008, it was approved by the FDA for use in breast cancer, against the advice of its advisory panel.” (source: Wikipedia) Say WHAT??? Against the advice of its own advisory panel???

How could something so bizarre happen? I went to read the February 22 2008 New York Times article (http://tinyurl.com/yu3xx5) dealing with this subject (notice that it’s printed in the “Business” section of the paper…this will make sense as you read on…). An excerpt: “FDA approval for late-stage cancer treatments is usually contingent upon data showing a drug extended, or improved the quality of, patients’ lives. Avastin showed neither in a study, according to Genentech’s application.” NEITHER? Ehhhh?

Genentech, the pharmaceutical company that produces Avastin, showed that this drug “slowed tumor growth, without actually increasing life expectancy.” Contrary to what we read in this particular New York Times article, however, the FDA decision has a lot of breast cancer advocates and organizations very worried. And with good reason. Take a look at this February 16 2008 Science Daily article: http://tinyurl.com/2a33u7 Fatal seizures? Brain swelling? If you aren’t convinced yet, read this NY Times August 24 2007 article: http://tinyurl.com/yvuozf The news is sobering indeed. I wouldn’t go anywhere near Avastin.

Why am I suddenly interested in this drug? Well, I became concerned after reading a few Science Daily articles about it. It is also being discussed by myeloma patients right now. So today I checked to see if there were any clinical trials, and yes, there are currently seven trials testing bevacizumab on myeloma patients (relapsed and refractory…), mostly in combination with other drugs (bortezomib and so on). And there are 96 breast cancer and Avastin clinical trials. 96? Oh yes, I admit to being concerned, not for myself but for all the patients who are in clinical trials testing drugs with unknown side effects in the long run. And the short-term side effects are scary enough, as we have learned from the Science Daily articles.

A recent Ralph Moss report focused on the Avastin issue: http://tinyurl.com/2edftu An excerpt (but please go read the full report, it’s excellent on many MANY levels): “On Friday, Feb. 22, 2008, top administrators of the Food and Drug Administration (FDA) approved the drug Avastin for the treatment of advanced breast cancer. Avastin, which has already been approved for colon and lung cancer, is controversial because it has never been shown to extend overall survival (OS) in breast cancer patients. It has been shown to improve disease-free survival (DFS) by as much as 5.5 months, but disease-free survival is not by any means the same thing as overall survival. A patient receiving Avastin may have a 5.5 month improvement in disease-free survival yet still die at approximately the same time as someone who did not receive the drug.”

Need I mention that Genentech’s stock, which had been declining, according to a February 23 2008 New York Times article (http://tinyurl.com/26zts4), after the FDA approval…all of a sudden rose more than 8 percent? Money, profit, and more money…but who CARES about the patients??? Certainly not the CEOs whose pockets are being lined with blood money.

Ralph Moss ends his report attacking the FDA’s double standards: on the one hand, this agency is always ready to squash any promising CAM (complementary and alternative medicine) treatments, on the other, it gives a “free pass” to a big pharma company “for a drug that has yet to be proven to do anything significant for breast cancer patients.”

In Moss’ words, the “FDA has once again significantly lowered its standards for drug approval. If it proposed doing so across the board, including taking a more even-handed approach to CAM treatment, that would be the basis for an interesting discussion. But what FDA is doing is permitting a lower standard for the expensive products of Big Pharma, while remaining wary of all non-toxic or non-patentable agents. So, whatever happened to the level playing field that a former director of the National Institutes of Health (NIH) promised the CAM movement back in 1992? Gone with the wind.”

But wait, it isn’t all doom and gloom out there. Curcumin inhibits angiogenesis. No kidding. There are 85 studies in PubMed dealing with this topic. Not one. Eighty-five. I have read a few of them, myself. Oh, and so does resveratrol. But this is material for at least another post. I will leave it at that…for now.

Concluding thought: do we really need to strangle a tumour with drugs that are toxic, potentially fatal (some women have already died from Avastin) and outrageously expensive?

Need an excuse to drink coffee?

March 2, 2008 / / 5 Comments

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 10^th 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!

Hypoxic tumour cells are resistant to chemotherapy and radiotherapy. Eh!
Hypoxia stimulates IL-8, which is involved with cancer progression (including myeloma progression, as we know from a previous post).
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!