A blogging friend reminded me about the EGCG-Velcade study published on February 3^rd 2009 in “Blood,” and that I posted about here on February 4^th. Sherlock (grazieee!) retrieved the full study for me…but then I put it on my desktop and promptly, uhm…forgot about it. That happens. Oh well.

 

At any rate, this morning I read through it to see if there was anything I could add to what we know from the abstract (http://tinyurl.com/c9ppr2). There is.

 

Read this (BZM, by the way, is the acronym for bortezomib, marketed as Velcade): when BZM and EGCG were added together, the cell killing by BZM was completely prevented and cell survival remained at 100% […]. Yikes! This occurred even at low EGCG concentrations. Scary.

 

Another interesting discovery. This study’s findings contrast with previous reports about the cytotoxic (=toxic to cells) effect of EGCG on myeloma cells. The researchers only noted weak cytotoxic effects starting at 20 microM, which become somewhat more pronounced when drug exposure times are increased from 48 to 72 hours. Interestingly, even under conditions where EGCG is slightly toxic, it is still able to potently antagonize the cytotoxic effects of BZM. For example, in U266 cells, 20 microM EGCG alone reduces viability by 20% after 48 hours, and 10 nM BZM reduces viability by >95%—yet, when the two drugs are combined, viability is still only reduced by 20%. By the way, U266 is a myeloma cell line frequently used in these studies. Well, I must say, this bit of news is not encouraging AT ALL…Well, let’s go on.

 

The inhibiting effect of EGCG against bortezomib was observed also in vivo (nude mice with myeloma tumours, poor dears). I don’t need to go into any details, suffice it to say that the in vitro results were confirmed in vivo, too.

 

The researchers tested the antioxidant activity of EGCG to see if that could be the cause of its bortezomib inhibition, but no, that wasn’t it. They did confirm that EGCG is a powerful antioxidant, though, which is good news for green tea drinkers not on Velcade.

 

EGCG’s inhibiting activity is instead apparently due to the presence of boronic acid in BZM: The severe antagonistic effect of EGCG appeared to require the presence of the boronic acid moiety in BZM. Proteasome inhibitors that did not contain any boronic acid were not affected by EGCG. So EGCG has a problem with boronic acid, not proteasome inhibition per se.

 

Ah, in the Discussion part I read something that I didn’t know: Interestingly, it has been reported earlier that vitamin C, a 1,2-diol containing compound as well, is able to antagonize cell killing by BZM. Apparently, vitamin C reacts with the boronic acid contained in bortezomib and, like EGCG, inhibited its cancer killing effect. Not good. Another word of caution: if you are taking Velcade right now, please see also my report on dietary flavonoids and Velcade (scroll down my Pages on the right).

 

Well, this study certainly supports the importance of giving your cancer specialist a list of all the supplements that you would like to take. Especially if you are following a conventional course of treatment, and even more especially (!) if said treatment includes Velcade.

 

The study concludes: In humans, EGCG concentrations of 5–8 microM can easily be achieved after the ingestion of capsules containing GTE (polyphenon E). We therefore have no doubt that our discovery is highly relevant for clinical considerations and would strongly urge patients undergoing BZM therapy to abstain from consuming green tea products, in particular those widely available, highly concentrated GTEs that are sold in liquid or capsule form.

 

In conclusion, if you are currently taking Velcade, do not drink any green tea or take EGCG or vitamin C. You might feel better, but the anticancer effect of Velcade, unbeknownst to you, is probably being severely blunted, if not entirely obliterated. Not good!

 

By the way, I was so focused on the curcumin cell membrane ion channel studies that I completely missed celebrating my two-year blogiversary (=blog anniversary…I just coined a new word…or did I?) on March 17! Has it already been two years? Yep. Amazing how time flies…

This is a sort of continuation of yesterday’s post. In his comment, Peter asked an excellent question…my answer is that he is right, that these studies may not help us in practical terms right now, but they do point to the possibility that there is more to the curcumin picture than its well-documented poor bioavailability (when administered orally). The evidence that there may be other mechanisms at work seems to be accumulating…that is, unless I have completely misunderstood the studies that I have been reading recently!

 

The 2006 study (abstract: http://tinyurl.com/awyvv9) that I want to discuss today was sent to me recently by a friend (grazie!). It examines the link between the anticancer effects of dietary compounds and ion channels, which are membrane-bound proteins […] that are present on the surface of various cancer cells and tissues. Heh, and I thought cell membranes were difficult!

 

The activity of these ion channels is essential, it appears, for the progression of cancer…and metastasis. When certain ion channels (VPSCs, or voltage-gated sodium channels) are upregulated while others (VGPCs, or voltage-gated potassium channels…er, don’t ask!) are downregulated, in fact, cancer cell membranes get all excited, in line with such cells’ ‘hyperactive’ behaviour. The activity of ion channels has been found to control/enhance a variety of cellular behaviours that would be involved in the metastatic cascade. Oh boy.

 

The researchers therefore suggest that ion channels may be a major target for the anti-cancer effects of some natural compounds. By the way, an explanation of ion channels can be found at “Ion channels for beginners”: http://tinyurl.com/cae5b6 (see “Things ion channels do,” in particular). And the term “voltage-gated” is explained here: http://tinyurl.com/2lpqmo

 

At any rate, the main point is that the researchers set out to see if ion channels could be affected by a few well-known anticancer dietary compounds. What they discovered is significant, since, as I understand matters, when ion channels are affected, the various processes that lead to cancer progression/mestastasis are essentially stopped.

 

Well, as it turns out, resveratrol affects ion channel activity, thus reducing the excitability of metastatic cancer cells. So does curcumin, even though more evidence is needed for the latter, according to the study. The list of ion channel-affecting substances goes on: capsaicin, genistein, ginseng…ah, also omega 3 PUFAs and zinc. In fact, thanks to this study, genistein moved to the top of my to-be-tested supplement list.

My own ramblings. Okay, we know that very little curcumin ends up in the bloodstream, plus a lot of it gets transformed into metabolites that may not be as powerful as the original stuff (although that is an unresolved question, as we have seen in previous posts)…but just yesterday we learned that curcumin affects cell membranes…and today we find out that curcumin most likely affects ion channels, which are involved in cancer progression and metastasis. Well, the only possible conclusion, in my view, is that curcumin and other poorly bioavailable substances may work in ways that have yet to be explored. And this is all very encouraging to me, an enthusiastic curcumin-taker with smoldering myeloma…

Sherlock (grazie!) sent me the full curcumin/cell membrane study (abstract: http://tinyurl.com/atknp7), the one that I mentioned in my March 9 2009 post. What was I thinking? What do I know about gramicidin channels of varying lengths and bilayer deformations? Er, not much, I’m afraid…

But…I tried. And, incredibly!, I managed to glean a few pearls. As follows.

 

Despite intense interest in the physiological effects of curcumin, a general mechanism for its action has not been identified. Studies of curcumin have shown that it influences structurally unrelated membrane proteins across several signaling pathways.

 

So the business about curcumin possibly affecting membranes had been hypothesized in previous studies. In a moment of utter madness, I actually glanced at a couple. A 2008 study (see http://tinyurl.com/buza49) suggested that curcumin affects the function of membrane proteins. But these changes had not been studied in detail until Prof. Ramamoorthy and his group examined them with solid-state nuclear magnetic resonance techniques (see: http://tinyurl.com/cvvzb3).

 

After trying to make heads or tails of quadrupolar coupling, acyl chains, anionic amphiphiles and all the other incomprehensible (to me) thingies mentioned in Prof. Ramamoorthy’s report, I gave up and jumped directly to the Discussion…parts of it were beyond my comprehension even after several read-throughs. But a few things were fairly clear.

 

An interesting suggestion concerns liposomal curcumin: It has also been reported that liposome-encapsulated curcumin has greater bioavailability and in vivo efficiency. Our results suggest that the incorporation of curcumin into liposomes strongly enhances the stability of curcumin and may have a strong impact on the demonstrated greater effectiveness of liposomal curcumin.

 

Curcumin stuck inside a liposome (see: http://en.wikipedia.org/wiki/Liposome)….a simple (?) solution that sounds better (to me) than the enteric-coated capsule idea.

 

Important excerpt: Cancer cells treated with curcumin display some features typical of apoptotic cell death […]. However, other features of curcumin-induced cytoxicity […] are not typical of standard apoptosis and point to a direct action of curcumin on the membrane as the initial step in the cytotoxic effect of curcumin on cancer cells. Fascinating.  

 

In conclusion, this 2009 study is the first to detail the real and dramatic changes caused by curcumin in cell membranes. I found most of it difficult or even impossible to interpret, but the parts that suggest that curcumin’s anticancer activity begins at the atomic level might help explain why this yellow-orange powder keeps some of us stable in spite of its well-documented poor bioavailability. Of course, given my lack of scientific training, this is just my own guesswork!

Occasionally I come across more substances that inhibit, or may inhibit!, IL-1 beta, which is a key SMM-MM progression factor (see my page on IL-1 beta or my early February posts). Just the other day I found another one: oats! Or, more precisely, polyphenols from oats called avenanthramides. A 2008 study on the prevention of atherosclerosis (see: http://tinyurl.com/croz5k) tested human aortic endothelial cells with the purpose of determining if the mechanism of inhibitory effect of these polyphenols from oats on the expression of proinflammatory cytokines is mediated through modulation of nuclear factor-kB-dependent transcription.

 

This study (grazie, Sherlock!) mainly examines a synthetic form of avenanthramides called CH3-Avn-c, which, to be honest, is of little interest to me (ALL I need is another pill or capsule, argh!). I am more interested in the following:

 

Taken together, our results demonstrate that Avns, specific polyphenols from oats, possess potential anti-inflammatory properties, which may lend to their potential beneficial effect in the prevention of atherosclerosis through inhibition of NF-kB activation. It is interesting to note that oatmeal bath has been used for skin conditions such as eczema, poison ivy, insect bites, sunburn, and shingles, where inflammation is known to be the main culprit. Our findings are in line with the observation of several naturally occurring polyphenols in foods, spices, and herbs, such as curcumin, myricetin, quercetin, resveratrol, and green tea constituent (–)-epigallocatechin-3-gallate (EGCG), all of which have been suggested to have health benefit effects through long-term consumption by modulating NF-kB activity.

 

Long-term. Hmmm. This adjective is a good reminder that there are no quick fixes with natural extracts. Patience is key. If something doesn’t work immediately, perhaps we shouldn’t discard it right off the bat. Well, unless our markers worsen, of course. That’s a different story…

 

Another important excerpt: Our data also point to the potential benefit of including oats and oat bran in daily meals over the long term. Oat products not only are known to reduce blood cholesterol, but also may help to suppress the inflammatory process associated with the development of atherosclerosis. “Long term” is mentioned again in this paragraph. Eh. We are also reminded that oats have a beneficial effect on blood pressure and are a rich source of many nutrients and antioxidants including vitamin E, phytic acid, and unique polyphenols, avenanthramides.

 

Well, including oats in our diet may not do much to inhibit IL-1 beta in the short term (no quick fixes!), but they are good for us in so many other ways. I am going to eat more (organic) oats from now on. In fact, I just had a bowl of (organic) oatmeal and flaxseed for lunch!

 

A blog reader sent me this list. Enjoy!

 

Church Bulletins

 

The following items actually appeared in church bulletins or were announced in church services:

 

The Fasting and Prayer Conference includes meals.

 

The sermon this morning: “Jesus Walks on the Water.” The sermon tonight: “Searching for Jesus.”

 

Our youth basketball team is back in action Wednesday at 8 PM in the recreation hall. Come out and watch us kill Christ the King.

 

Ladies, don’t forget the rummage sale. It’s a chance to get rid of those things not worth keeping around the house. Bring your husbands.

 

The peacemaking meeting scheduled for today has been canceled due to a conflict.

 

Remember in prayer the many who are sick of our community. Smile at someone who is hard to love. Say “Hell” to someone who doesn’t care much about you.

 

Don’t let worry kill you off–let the Church help.

 

Miss Charlene Mason sang “I will not pass this way again,” giving obvious pleasure to the congregation.

 

For those of you who have children and don’t know it, we have a nursery downstairs.

 

Next Thursday there will be tryouts for the choir. They need all the help they can get.

 

The Rector will preach his farewell message after which the choir will sing “Break Forth Into Joy.”

 

Irving Benson and Jessie Carter were married on October 24 in the church. So ends a friendship that began in their school days.

 

A bean supper will be held on Tuesday evening in the church hall. Music will follow.

 

At the evening service tonight, the sermon topic will be What Is Hell? Come early and listen to our choir practice.

 

Eight new choir robes are currently needed due to the addition of several new members and to the deterioration of some older ones.

 

Scouts are saving aluminum cans, bottles, and other items to be recycled. Proceeds will be used to cripple children.

 

Please place your donation in the envelope along with the deceased person you want remembered.

 

The church will host an evening of fine dining, super entertainment, and gracious hostility.

 

Potluck supper Sunday at 5:00 PM–prayer and medication to follow.

 

The ladies of the Church have cast off clothing of every kind. They may be seen in the basement on Friday afternoon.

 

This evening at 7 PM there will be a hymn singing in the park across from the Church. Bring a blanket and come prepared to sin.

 

Ladies Bible Study will be held Thursday morning at 10 AM. All ladies are invited to lunch in the Fellowship Hall after the B. S. is done.

 

The pastor would appreciate it if the ladies of the congregation would lend him their electric girdles for the pancake breakfast next Sunday.

 

Low Self-Esteem Support Group will meet Thursday at 7 PM. Please use the back door.

 

The eighth-graders will be presenting Shakespeare’s Hamlet in the Church basement Friday at 7 PM. The congregation is invited to attend this tragedy.

 

Weight Watchers will meet at 7 PM at the First Presbyterian Church. Please use large double door at the side entrance.

 

The Associate Minister unveiled the church’s new tithing campaign slogan last Sunday: I Upped My Pledge–Up Yours.

Well, well, I just happened upon a lovely bit of news. Are you ready?

 

The MD Anderson curcumin myeloma clinical trial is not THE only one. Yep, that’s right. Another trial is being held right now in Australia. Well, okay, technically, it’s a MGUS, not MM, curcumin trial, as we will see in a second.

 

Let’s see, you can access the PDF file that provides some information about the trial (an interesting read, by the way), but for some reason it doesn’t seem to work unless you do a Google search (for instance, the words curcumin myeloma clinical trial Australia should bring up the correct Dove Press article).

 

OR you can click on this HTML link: http://tinyurl.com/crkjy3. Then click on the PDF link at the top of that page. You can then download the PDF file onto your computer.

 

OR (!) you can do another Google search for the title of the study “The potential role of curcumin (diferuloylmethane) in plasma cell dyscrasias/paraproteinemia.” I’m very sorry that I cannot provide a direct link (as I said, it doesn’t work, not for me anyway). But this search operation will take only a few extra seconds of your time.

 

If you don’t want to go to the trouble, though, then just read the following synopsis. The abstract tells us that Preliminary results from our pilot study show a drop of between 5% and 30% serum paraprotein in patients taking curcumin compared with patients on placebo. Thirty percent??? Holy cats and dogs! That’s Giovanni Allevi music to my ears…sweet!

 

The Australian researchers favour early intervention in MGUS patients to reduce the paraprotein load. I am in favour of that, too, but only if said intervention is made with non-toxic natural extracts. As in this case.

 

Toward the end of the article, we get to the relevant part: We are conducting a single blind randomized controlled pilot study on 25 patients with paraproteinemia. Entry criteria included patients defined as having MGUS ie, the presence of a serum paraprotein (greater than 8 g/L and less than 40 g/L) with the exclusion of multiple myeloma. These patients are being monitored for a 6 month period of curcumin or placebo therapy.

 

I almost got teary when I read what followed: Curcumin or placebo is being administered orally as a 2 grams twice daily regimen. After one week on curcumin, there has been a drop of between 5% and 30% serum paraprotein in some patients, compared to controls […]. After 3 months of curcumin therapy, these reduced levels have remained suppressed. These exciting findings have prompted a double-blind, randomized, controlled trial. The benefits of the fall in paraprotein is uncertain. How long these reduced levels will remain suppressed and what the clinical benefits are, remain to be seen. As a natural product, it has exciting potential in the treatment of plasma cell dyscrasias. Only TWO grams of curcumin??? YAY!!!

I say, this is very exciting news indeed. Another trial! Plus, the preliminary results are bloody excellent. Hoppity hop! Needless to say, I have a million questions that I hope will be answered soon. For instance, I wonder what type of curcumin these patients are taking, how they are taking it, blablabla. Rest assured, as soon as I have any news, I will post it. Good or bad, as always…but hey, how could it not be good?!!!

Yesterday a blog reader/friend (thanks!) sent me a funny e-mail. I forwarded it to family and friends, but decided that I had to post about it, too, even though I had planned to post on a more serious topic today. Well, “serious” can wait until tomorrow…besides, er, this could be seen as a continuation of yesterday’s “bathroom” post….okay, here goes…

 

 

 

First image. Imagine that you are at a party. On the 10^th floor of a high-rise building.

 

And then you have to pay a visit to the bathroom…

 

You open the door….

 

And find….THIS.

 

It’s just a painted floor, of course, but doesn’t it make you wonder if you would have the guts to step inside this high-rise bathroom?

 

 

 

 

 

Second and third image.

 

This woman is getting ready to enter a public toilet in Houston, Texas.

 

Okay, you’ve seen the outside (above, on the right), now check out…the inside (on the left)…

 

It’s made entirely of one-way glass. Nobody can see you from the outside, but when you are inside, it’s like sitting inside a clear glass box.

 

Now…truthfully…would you…indeed, COULD you…???

Throughout the years, I have bought my cats what I have considered to be fantastically fun cat toys. “They’re going to love THIS one,” I would stubbornly repeat to myself. Well, “this one” usually joined the other discarded toys in a basket. I guess my idea of “great cat toy” doesn’t coincide with theirs. But even though I now almost never buy any cat toys (empty cardboard boxes are much more fun, you see), I do occasionally fall for a new, uhm, “great” toy.

 

My cats’ initial reaction is usually satisfactory. They will look at it, sniff it and even pretend to be interested for a moment or two. If I’m lucky, they will politely bat it around the room for a few seconds. Then they will look at me disdainfully, as though saying “is that IT? Well, phooey to you, you foolish tall creature,” and strut off, with their tails straight up in the air.

 

But there is one toy that has managed to keep my kitties’ interest alive. It’s a dumb little thing, really, something that you could easily make yourself: a small flat piece of leather shaped like a squished mouse (the shape, I suppose, is intended for us dumb humans; I’m sure cats wouldn’t notice if it were the outline of an elephant or a ladybug) and stuck on the end of a piece of string. I call it “mousie.” All of my cats have loved and enjoyed playing with mousie.

 

Peekaboo, my youngest kitty is no exception. She goes absolutely bonkers over mousie. At night, Peekaboo and I frequently play with mousie until I have had enough. At that point, I distract her somehow (not easy), then, unbeknownst to her or hah so I think!, I hastily shove mousie inside my pyjama pocket and try to look nonchalant. She usually spends a few minutes frantically hunting for mousie all over us and our bedroom but finally gives up and settles down in my lap. As soon as I get the chance, I sneak out of bed, slink over to the bathroom, lock myself inside and hide mousie on top of the bathroom cabinet. Out of sight. Phew. There is NO way Peekaboo can figure out where mousie is. Right?

 

Wrong.

 

For the past week or so, I have not had one single peaceful, er, session in the bathroom, not even to clean out the litter box. As soon as I shut the door, Peekaboo throws herself forcefully against it. She is actually able to open it (if it’s unlocked). When she cannot get in, though, she scratches frantically at the door and howls piteously…a hyena being slowly and painfully strangled could not possibly emit a more horrible noise…I am convinced my next door neighbours think that we torture our cats in atrocious ways…

 

At first, I just couldn’t figure it out. She’d never before been interested in the bathroom. Besides, she doesn’t howl in front of the bathroom door when Stefano is inside, so what is her problem with MY being in there? I imagined it could possibly be a form of “separation anxiety.” Yes, I even got a bit emotional at the thought that my sweet little baby just couldn’t stand losing sight of her mommy and felt the need to be with me every instant of the day. Oh, I know, I know…

 

Then a faint light went on in my brain. Point 1: She must somehow have found out that mousie is inside the bathroom (and no, it is not a catnip toy). Point 2: I am always the one who plays mousie with her, not Stefano…so that is why she doesn’t care one whit about HIS being in the bathroom. Mystery solved.

 

But it gets worse. The cunning little creature is now trying to work out how to jump from the toilet to the top of mousie’s cabinet. Yesterday I caught her stretching her body upwards as far as she could, as if measuring the distance. When I walked into the bathroom, though, my petite drama queen threw herself on the floor, showing me her fuzzy little tummy and chirping seductively…as though not interested in anything but me…

 

Okay, clearly, it was time to change hiding places. Ah, no, wait, I had a better idea. Last night I put mousie on a bookshelf in my study, way up high, out of a cat’s reach, but making sure that Peekaboo had seen where it was. Will my kitty’s Sarah Bernhardt performances finally come to an end?

 

Hmmm, I doubt it. She has already let me know that she is on to me, that she is perfectly aware that mousie isn’t REALLY on my study bookshelf. “It’s still in the bathroom,” she informed me this morning with an affronted look. (But it’s not, it’s in my study, I swear!)

 

My (bathroom) peace has probably vanished…forever.

Hehe, I love it. Curcumin, the disciplinarian! According to yesterday’s Science Daily newsletter (see http://tinyurl.com/cgxhcp), a recent study shows how curcumin actually works inside the body, at the cell membrane level. Extraordinary. Curcumin actually gets inside our cell membranes, making them more orderly, thus improving the cells’ resistance to infection and malignancy. It acts like a disciplinarian: “behave or else…!!!”

 

My favourite quote from the article: The [cell] membrane goes from being crazy and floppy to being more disciplined and ordered, so that information flow through it can be controlled […]. Amazing, huh? 

 

Interesting titbit: the lead scientist in this project, Prof. Ramamoorthy, As a child in India, […] was given turmeric-laced milk to drink when he had a cold, and […] breathed steam infused with turmeric to relieve congestion.

 

I asked Sherlock if she could get her hands on the full study, but a quick glance at the abstract (http://tinyurl.com/atknp7) tells me that it may be way over my head. I will give it a whirl, though. One important excerpt from the abstract: curcumin has a strong effect on membrane structure at low concentrations. At low concentrations…hmmm, this might help explain a few things…

My cousin sent me the link to this video…I laughed out loud…had to share: http://tinyurl.com/djvk2d