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.

34 Comments

  1. Hi Margaret,
    I will be very interested to hear how you get on with Green Tea. I started drinking cups of Green Tea with lemon (it tastes better) about 6 months ago. I usually have between 1 & 6 cups a day. I have noticed that the problem I have had with dry, sticky, eyes is alleviated with Green Tea. Like you, I think the benefits are likely to be much wider than just eyesight and I think it could be even more important than curcumin.
    Paul

  2. Hi Paul,
    did you have any blood tests done before and after you started drinking Green Tea? By the way, if you drink Green Tea, instead of taking supplements, be sure you drink Japanese Green Tea and not Chinese Green Tea. Béliveau and Gringas in their wonderful book on food and cancer (see Margaret’s post on this), not only devote a whole chapter to Green Tea, but make it quite clear that Japanese Green Teas are more effective than Chinese ones.
    Have a nice day,
    Sherlock

  3. I too was told that the best green tea is japanese
    “matcha” tea….but I am not able to find matcha tea (organic)
    in stores .Where do you buy japanese organic matcha in Florence?

    I am planning to order it through internet
    thanks
    carla caregiver to husband dx with NHL and CC

  4. Non sono certa se questo té sia in vendita presso Naturasì, dovrò controllare, ma ho letto che si può trovare (non so se sia bio, però) alla “Via Del Té” in piazza Ghiberti. Hanno anche un sito web.
    Carla, potresti darci il nome del sito da cui lo ordini? Grazie!
    Margaret
    🙂

  5. Thanks a lot, Margaret, for bringing this study to my attention. Just wanted to add that your stance on taking seemingly helpful, non-toxic agents is most reasonable. Best wishes…

  6. Margaret, il sito e’ http://www.spaziomusa.com, dicono che vendono
    matcha organico prodotto da Aoi in Aichi Giappone…al prezzo
    di 25 euro,…vendono anche gli accessori di bambu’ per dosare
    e mescolare il matcha…
    da Naturasi’ in via Masaccio ci sono stata pochi giorni fa e
    non l’ho trovato,il negozio che nomini in piazza Ghiberti non lo
    conoscevo, provero’ a chiedere se hanno il matcha organico ..
    finora abbiamo usato il te’ verde Amothe organico della Vegetal Progress,
    ma sento dire che il matcha e’ migliore..
    carla

  7. Hi Margaret,

    The effects of EGCG are apparently potentiated by taking Vitamin C at the same time; EGCG is best absorbed in an acid environment, hence the directive to consume it under fasting conditions, and the addition of ascorbic acid is said to further increase its bioavailablity.

    Marylynn

  8. Hi Sherlock,
    To be honest, I can’t remember exactly when I started drinking green tea but I was diagnosed with MGUS in May 2005 and began taking supplements at the end of November 2005. I have never really treated tea as seriously as the other supplements and, for a long time, I thought my eyesight had benefited from Omega 3. Now I’m more inclined to think it is green tea. Perhaps it was both! I thought I had something like Sjogren’s Syndrome but it’s fine now – as long as I keep up the tea and omega 3.
    I do have blood results from before and after although I’m uncertain about the figures for the first year because they originally measured total IgG – then just the paraprotein element. However, it does seem that my paraprotein level dropped from 26-27 to 21-23 around August 2006 and it has been fairly constant ever since.
    Thank you for the advice on Japanese vs Chinese green tea. I’m not sure what type I drink. It’s Clipper Brand and it doesn’t say on the packet. I suspect it’s China tea – although it is sourced from many countries.
    Best wishes,
    Paul

  9. Dear Margaret,
    Is there a way to contact you directly and privately.
    I have MGUS and have a specific question about those bones scans.
    thank you
    I hope that you can see my email to respond to me.

  10. Carla,
    according to Beliveau and Gingras – whose book is published in also in Italian – the best Japanese green tea is not Matcha, which is just a little better than the Chinese teas. The best tea is called SENCHA-UCHIYAMA. Other similar excellent teas are Gyokuro 1, Sencha 1, Sencha 2, and Gyokuro 2. All these are the best teas in terms of anticancer properties. At Naturasi I found a Japanese tea called simply Sencha, but I’m not sure it’s Secha1 or Sencha2, because Sencha, in Japanese, simply means green tea.

    Paul, when you say ‘paraprotein level’ what do you refer to? I mean, 21-23 is a percentage, isn’t it? Do you have a measure of your paraprotein expressed in gr/dL? Anyway, your 21-23 level is really excellent. How high are your total proteins?

    have a nice day! Sherlock

  11. Hi Sherlock,
    They now express paraprotein in g/dL here (rather than percentage or m-spike). I’m not sure I agree that 21-23 g/dL is excellent. I would love to get it below 20 and to see a continual decline. I won’t be relaxed about it unless it goes down to single figures. Then I might start to think I’m winning :-).
    My total protein bounces around a lot and seems to bear little relationship with the paraprotein. I wouldn’t even say it ws directly correlated. Over the last year it has ranged from 85 – 97.
    My albumin did go as low as 41 once but 45-46 seems normal. Interestingly, my good immunoglobulins (IgA and IgM) seem to be creeping back up over the last 6 months. I hope that’s a good sign.
    I sent Margaret all my numbers about 6 months ago and you are welcome to look at them if you wish.
    Best wishes,
    Paul

  12. Hi Paul,
    something is so strange with your numbers! When I said ’21-23 is very good’ I was sure that 21 was a percentage! 21 g/dL is awful, from my point of view. I’m sure we are talking of different measures…
    In Italy, for instance, total proteins are (normal range) between 6 and 8.8 g/dL. So there is nothing like 85-97. Same for paraproteins: either 21% or, say, 2.4 g/L
    Anyway, total proteins are certainly related to paraproteins. The highest the worse.
    Last, it’s fantastic that you have IgA and IgM creeping back. Those proteins usually get lower and lower as monoclonal IgG go up.
    Sherlock

  13. Soory Sherlock – I was being dumb – I should have written g/L.
    My figures are: (TP first, Monoclonal IgG 2nd, albumin 3rd – all g/L)

    2/06 89, 26, 46
    5/06 93, 27, 45
    9/06 87, 23, 43
    1/07 91, 22, 43
    5/07 85, 24, 41
    7/07 87, 21, 46
    8/07 97, 23, 45 (new hospital)
    12/07 90, 22, 46
    1/08 96, 23, 45

    The paraproteins are also g/L – not %ages.

    I had a 2-day cold just before my last test so that might be why my IgA went up but I’m hoping it wasn’t a one-off.

    Best wishes,
    Paul

  14. Ok, then it’s easy. In Italy it’s g/dL and that means that your results make perfectly sense putting the necessary comma. In Italy, for instance, your more recent result would be 9,6 for total proteins and 2,3 for the monoclonal IgG. Having gone from 2.7 (May 07) to 2.3 (January 08) it’s excellent in my opinion.
    have you tried curcumin?

    Sherlock

  15. All I can say is “wow”, this is great information. What we do without our Angel Margaret.

    I have melanoma but alot of what is being discussed is a benifit for me. I am having a hard time with the pubmeds, they are very hard to understand, why can’t they use simple words. I have to read them many times and hope I am getting it right.

    You all rock

    Keep the faith, we all have too much to live for.

  16. Am I the only one who gets too buzzed from green tea and cannot sleep and get all hyper? Does the concentrate not have this effect? Winnah

  17. Hi Sherlock,
    I started taking curcumin in Jul 07. Not as much as you – only 2 x 500mg/day with Bioperine – “Doctor’s Best”. In the past I have had problems with an inflamed stomach so I don’t believe in taking too much of anything. As an old friend of mine used to say “hasten slowly” :-).
    I have had 2 significant (>10%) declines in my paraprotein since I was diagnosed. The first (from 27 to 23) followed a glorious 5-week holiday in Australia when I was taking no supplements other than B12. Since I was taking B12 both before and after the holiday with little effect, I put the benefit down to sunshine, relaxtion, and good company :-).
    The second decline (from 24 to 21) was immediately after going on a gluten free diet – although my levels have increased a little since then and I have maintained the diet. However, the important thing is that I feel better now. I think reducing paraprotein levels (if indeed it is possible) will be a very long process (years). I suspect the problem took years to develop in my case so it will not be easy to reverse. If anyone has a quick fix I would be very happy to hear it. Otherwise, I will be more than content if I feel well and my levels remain stable.
    I understand that you have had a long period of good health and paraprotein stability and that, in itself, must give us all reason for hope.
    Best wishes,
    Paul

  18. to Pam Black: It sounds to me like you are reacting to the caffeine in the tea, which can be substantial. Life Extension Foundation sells a decaffinated green tea extract capsule that might be better for you. I gave it to my wife (Alzheimer’s patient) because she is very sensitive to caffeine. LEF sells both decaffinated and regular, so be sure what you are getting.

  19. Hi Paul,
    here is my experience. I’ve been living with Mgus for about 17 years (1988-2005). In nov. 2005 I was diagnosed SMM as the BMB revealed 70% of plasmacells.
    But my health status has not changed very much and I feel as good as I felt when I was Mgus.
    Since 2005 I have had 3 significant declines in my paraprotein level:
    the first (from 2,64 to 2,35) in January 2006. I also had an holiday in Marocco, but due to the stress of the diagnosis I didn’t enjoy it very much. What happened is that I took distance from a very stressful period of work. Also underwent an operation for a minor problem, which improved my general health.
    The second decline (from 2,55 to 2,27) in February 2007. In this case I do attribute the decline to the beginning (in September, when I was 2,55) of regular exercise (in a gym), something I’ve never stopped since then and which is very good for MMers’ bones too.
    The more recent decline (from 2,62 to 2,24) is of January 2008 and is due to curcumin.
    What I would like to stress is that the curcumin decline is the greatest of the three (-14,3%, while the other two are -10,9%).

    I’ve come to believe that if your MM is not an aggressive one, there are probably several ‘things’ that can ‘stabilize’ it.

    have a nice day,
    Sherlock

  20. Hi Wally,
    thank you for rising the issue of caffeine in tea. You’re absolutely right. As I drink a lot of coffee, it’s probably much better to get a tea extract without caffeine 🙂

    Sherlock

  21. Hello!

    Great stories and info here, from all of you!

    I would just like to add that we should be cautious buying the right stuff, whatever it is. And by “right” I mean really organic.

    There was a lot said and written about the toxicant effect of the chemicals used in agriculture. Be ware of them in any food or drink!

    Pam – I think if you only leave the tea in water for less then a 3 minutes the caffeine doesn’t start to secrete. Just a thought.

    Have faith everyone and best wishes!!

    Robert, Slovenia

  22. Hi Sherlock,
    It is interesting to compare notes and to see how important it is to live a healthy, stress free, life.
    What amazes me is that so many people seem to be stable with a paraprotein level in the low 20’s. As I have said to Margaret in the past, a stable situation is most unusual. If paraproteins have a half life in our bodies of 21-25 days, they must be being replaced at the same rate as they are being excreted. This implies there is some sort of feedback mechanism. I have asked many people about this and no-one seems to know the answer. When I asked my (quite eminant) haematologist last time, he ushered me out of his office rather quickly. However, if we can find the answer to this conundrum, I’m sure we will have a much better understanding how to keep the disease under control – or maybe even cure it.
    Best wishes,
    Paul

  23. Hi Paul,
    I’m very bad at math. Could you explain me as easy as you can this story of half-life, rates etc.? If I understand it I can ask my (also quite important) hematologist next time I see him. Any reference to the literature would also be very useful. Thank.

    Sherlock

  24. Hi Sherlock,
    Talk to Margaret because I think she knows quite a bit about this. We have discussed it by email several times.
    From what I understand, the current theory is that myeloma stem cells (capable of cloning) turn into differentiated myeloma plasma cells, which in turn produce the marker paraprotein immunoglobulins (IgG etc) in our blood.
    It also seems that the level of blood paraprotein is an accurate reflection of the tumour load.
    However, I understand that half the paraproteins are excreted by the liver every 23 days, or thereabouts. So, if our paraprotein levels are stable, the amount that is being excreted must be exactly equal to the amount that is being produced. The question is why? There must be some sort of feedback mechanism – possibly the same sort of homeostasis that keeps blood sugar levels constant in non-diabetics.
    I have not seen any reference to this in the literature. Perhaps I have mis-understood the situation.
    Best wishes,
    Paul

  25. Hi Paul,
    I was thinking at your 5 week holiday in Australia. Did you eat or drink anything special, that you don’t usually get where you live?
    Just an idea.
    S.

  26. Hi Sherlock,
    No, nothing special. I think it was just plenty of sunshine, fresh air, and getting away from this damned PC.
    Paul

  27. Hi COCOA has more EGCG then Green Tea and Turmeric & Green Tea enhance each other and Heated Oil with Turmeric enchances 10 fold and Vitamin C enhances Turmeric

  28. Hi Margaret and Sherlock and kitty,

    I am now 63, and was diagnosed with cll in 2007, Rai stage 2, at Mayo, among other places including dr.Rai. I had read about the green tea, EGCG study before going to Mayo and of course asked about it. at the time, 2007 the second phase, I believe, was on hold, but due to resume. I signed up, agreeing to stop using ANY green tea at all for at least six months. I did, and still the study did not commence. I sought the help of Dr. Raymond Chang in NY, Meridian Medical. org whom I had consulted several times before, (hematology and immunolgy). He found the type/strength they use at Mayo and got it for me. I began taking it. I can’t of course get anyone to correlate any of my blood work to what I have been doing. (2, 500 mg caps of this highly concetrated imported EGCG 2 x a day, equal to a zillion cups of green tea)
    I am stable, with symptoms, sweats, weight loss, fatigue etc. I also have chronic Squamous Cell Carcinoma, 5 surgeries on one ear over four years, and the two don’t do well together) I have however seen a drop in my awc. from the 14 – 12 to 10, just above the normal. no one comments however,, medical politics, not their study, not in study, no ‘controls’ I get it… but it’s frustrating none the less. I will of course continue to use the EGCG, and drink my usual 6 – 8 8 0z glasses of green tea with raw honey every day, almost my only beverage… love it.

    Dr. Chang also found a study that uses theophyllin for cll, I tried the pill form and it was too strong for me, but now use an old standby, elixophyllin, a liquid, used for ever as broncho dialator, CLL seems to cause thick mucous in some patients, I’m one, after three pneumonias and almost not able to breathe, that worked wonders, along with singulair, which I researched and switched to after I tore a shoulder using quinolones (antibiotics) and advair and nasocort, both contain steriods, . seems singulaire has also been used in some cancers. it’s main ingred seems to target leukotriens, also a player in cll.
    good source for CLL patients…www.clltopics.org Chaya is amazing and goes into a lot on alternative, plus trad … explains so one can understand. (searchable by substance, disease, trial etc)

    cox 2 inhibitors too, but usually perscrip which I can’t take, GERD…
    looking at Zyflamend for that. might also help some of the inflamatory pains … just have to find the time to check the individ ingreds agianst all of my other drugs and add ons.

    my bottom line is if something is not toxic, and might help, and reduces symptoms, I’m on line. so thanks,

    ps, have had no trad chemo etc, only IVig infusions once a month due to immunoglobulinemia and repeated pneumonias. seems to help too.

    wonderful cat you have there. take care and thanks, beth

  29. Dear Margaret

    I would like to indicate you the private website of Prof. Dr. med. Werner Hunstein:
    Apart from the personal medical/patient story of this german doctor, you can find up to date information (2010/2011) obout green tea and EGCG.

    Particulary interesting the part about of the combination – EGCG + piperine + vitamin C –

    http://www.hunstein-egcg.de/index.html

    http://bloodjournal.hematologylibrary.org/content/110/6/2216.full.pdf+html?sid=551dbf1c-248f-40cc-a533-96518398eae4

    http://www.ukgm.de/ugm_2/deu/ugi_hum/EGCG_Piperin_engl.pdf

    http://www.hunstein-egcg.de/Bieschke-en.html

    http://www.ncbi.nlm.nih.gov/pubmed/20221615

    Very interesting the article (2010) about diet in Transthyretin Amyloidoses. You can find here some good suggestions which could have general value also in multiple myeloma

    http://www.ukgm.de/ugm_2/deu/ugi_hum/PDF/FAP_nahrung_engl.pdf

    Best wishes
    R.

  30. I would like to add to my previous post an another recent article (August 2011) regarding green tea extract EGCG :
    It is an actual review about many practical aspects of how to handle EGCG and how to optimize bioavailability. Very interesting the combination – EGCG + Vitamin C + omega-3
    fatty acids –

    Epigallocatechin-3-gallate (EGCG) for Clinical Trials: More Pitfalls than Promises?

    Mereles D., Hunstein W. Epigallocatechin-3-gallate (EGCG) for Clinical Trials: More Pitfalls than Promises?. International Journal of Molecular Sciences. 2011; 12(9):5592-5603.
    http://www.mdpi.com/1422-0067/12/9/5592/pdf

    With best wishes
    R.

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