Reishi and multiple myeloma: full study

On July 30th, just before leaving for the U.S., I posted about Reishi, or Ganoderma lucidum, and its murderous effect on leukemic, lymphoma and MM cell lines. At the time, I had been able to read only the abstract.

Soon thereafter, a blog reader (thank you!) kindly let me know that the full study is available online: http://tinyurl.com/ljsbh7. Slight problem: my online copy (I hope this doesn’t happen to everyone!) comes to an abrupt halt at the end of page 7, which means that the final Discussion points are missing, as are the references. Very peculiar. As usual, though, Sherlock (grazieee!) came to the rescue by sending me the complete study, so I was able to fill in the missing bits.

Let’s see. Since the full study (or rather, most of it!) is online, I won’t make but a few comments. Reishi was tested against the above-mentioned cell lines together with other five herbs with known anti-cancer activities (see above link, the Discussion part, page 7) and was found to be the most active of all. It was especially effective against the blood cancer cell lines.

The following excerpt is from page 8, my mysteriously “missing” online page: Taken together, our study is the first to examine the effects of G. lucidum extract on a large panel of hematologic cell lines. Our results show that G. lucidum extract has activity against leukemia, lymphoma and myeloma cells and may be a novel adjunctive therapy for the treatment of hematologic malignancies. Further research is planned to isolate the triterpenoid constituent of G. lucidum (ganoderic acid) and to examine its anti-cancer potential.

I bought a Reishi extract while in the U.S. this summer and plan to test it, on myself of course!, at some point this winter. Interesting times lie ahead…I hope!

Ciclopirox olamine’s effect on leukemic and myeloma cells: the full study

At the end of July, right before the summer holiday, Sherlock (grazie!) sent me the full ciclopirox olamine study that I posted about on July 15th (the nail fungus treatment, remember?). I will skip through it and provide only a few excerpts for discussion, trying not to repeat the information that is already in the abstract (http://tinyurl.com/lkmrz5).

One important statement is that CPX-induced cell death was dependent on chelation of intracellular iron and the inhibition of the iron-dependent enzyme ribonucleotide reductase (all we really need to know about ribonucleotide reductase, or RNR, is that it is an appealing target in cancer treatment. An RNR-inhibitor, such as CPX, is therefore one of the good guys, so to speak…).

Let’s see. A number of pages are devoted to material and methods…skip skip skip…let’s go to the study results. Aha…I had wondered how/why ciclopirox olamine had been chosen among a number of other off-patent drugs with previously unrecognized anti-cancer activity. The mystery was solved in the full study: a screening process identified CPX as a substance that inhibited the growth of leukemic cells that display features similar to leukemic stem cells.

CPX was also identified as a survivin-inhibitor. Survivin is a protein that is also a regulator of cell cycle and apoptosis, and cancer cells contain high levels of it (for more info, you can search my blog for “survivin”). CPX was found to decrease the levels of survivin in leukaemia, myeloma and solid tumour cells. So far, so good.

Remember reading about “gross organ toxicity” in the abstract? Well, that “gross” business puzzled me, so I looked it up and found that, in pathology, a gross examination of a specimen is an examination done with the bare eye…without the use of any instruments, such as a microscope. Ah. Okay. So, unless I am way off base, it appears that treatment with CPX causes no harm to any organs or loss of body weight…based on a “bare eye” examination. CPX did, however, decrease tumor weight and volume in 3 mouse models of leukemia by up to 65%. Great!

More good news: CPX reduced the viability of primary AML cells and inhibited engraftment of primary AML cells in NOD/SCID mouse models. Thus, CPX appears cytotoxic to leukemia stem cells. A killer of leukemic stem cells! Yeah!

Well, I don’t want to go into too much detail…for instance, I could provide you with a detailed description of how CPX binds intracellular iron in cancer cells or how the inhibition of ribonucleotide reductase is functionally important for the cytotoxic effects of CPX or how CPX sensitizes cells to cytarabine. But I won’t. Too much information could give me AND you a stomping headache!

Just one last thing. In the Discussion part, we can read that CPX could be advanced quickly into clinical trial for patients with refractory hematologic malignancies. However, due to possible differences in iron pools between species, toxicities of CPX not apparent in rodents and dogs may become evident in humans clinical trials. Alternatively, CPX may be less effective in patients who have been heavily transfused and have very high levels of iron stores.

The issue of toxicity is a serious one, of course, and the authors point out that the potential hematologic toxicity and its safety will have to be carefully evaluated in phase I clinical trials. Well, an interesting study, for sure…

Manuka honey

Last month, while shopping in a local health food store on Cape Cod (Massachusetts), I came across a few jars of Manuka honey. They survived the crazy trip back to Firenze, and oh, I am sooo thrilled to have ’em!

Made by New Zealand bees, Manuka honey has very strong antibacterial, antifungal and antiprotozoal properties, see: http://news.bbc.co.uk/2/hi/health/3787867.stm. According to a New Zealand researcher, Prof. Molan, it can even tackle antibiotic resistant strains of bacteria – a growing problem for hospitals around the world. It apparently also has antioxidant, antiseptic and anti-inflammatory activity. I am now taking 1-2 tablespoons a day. Could this honey help me fight off the H1N1 virus, too? Not sure, but anything is possible. Besides, I happen to love honey…!

P.S. A quick note on the most recent addition to my daily supplement intake. I have decided to take ashwagandha (see my ashwagandha page on the right) for about a month. That’s not much time to test a new extract, true, but it’s all I have before my next set of blood tests. Okay, Tetris is roaring for my attention…I told you, this game is bloody addictive. I am up to level 6 now… 😉

Tetris = brain food

Are any of you Tetris-players? I ask that question because I used to be an avid one. I began playing Tetris in grad school and became quite good at it, actually, achieving high levels and huge scores. In case you have no clue as to what I am talking about, Tetris is a puzzle videogame created, oh, more than 20 years ago by a Russian guy. I once read that the name is a combination of the Greek prefix “tetra-“ and the creator’s favourite sport, “tennis.” Don’t ask…the “tennis” part makes no sense to me, either…

This is how it works: a random series of differently-shaped tiles drifts down your computer screen, one at a time…what you have to do is move and rotate these tiles in order to create a horizontal line with no gaps at the bottom of your screen. Whenever a full row of tiles is created, it disappears magically, poof!, and you score points. As the game progresses, and you get better at creating the lines, the tiles will fall faster and faster. As a beginner, of course, you fumble about, creating lines with gaps that of course do NOT disappear…so the rows keep piling up and filling your computer screen until you lose the game.

This description must sound totally boring. But I can assure you that this game is instead totally addictive…and there is more…

Just yesterday I discovered that Tetris is excellent fodder for the brain. Aha! Now I know why I was so smart in grad school! 😉

A September 1 Science Daily article (http://tinyurl.com/mmlkzk) reports on an experiment conducted on adolescent girls divided into two groups. One group played Tetris for three months, the other did not. Details can be found at the above link.

What I found fascinating were the conclusions: the girls who played the game showed greater brain efficiency, consistent with earlier studies. And certain parts of the brain, those associated with critical thinking, reasoning, and language and processing, developed a thicker cortex. Now, what does having a thicker cortex mean? The researchers have no idea, actually: How a thicker cortex and increased brain efficiency are related remains a mystery.

Okay, setting aside the baffling thicker cortex for now, the point is: if I can do something easy and enjoyable AND increase my brain’s efficiency…well, why the heck not? I stopped playing Tetris after being awarded my Ph.D. At the time, I had a hectic work schedule and was too tired/busy to play computer games. I have played it on occasion since then but have never been able to reach my previous high levels, which might be proof that you can learn a skill but also forget it without practice…rather like a foreign language that you studied in high school years ago…

All that is about to change. Tetris, here I come…again! My brain could use a little extra boost to help me understand some of the more obtuse scientific studies still lying on my desktop, waiting to be read…

Update: after years of NOT playing, or rather, after years of playing a game only occasionally, I still got up to level 3 on the first try…not bad, I guess. My goal now is to beat my all-time high score…I need more practice for that…

MGUS may be linked “only” to some serious diseases…

I am slowly going through my still unopened Science Daily updates…the August 27 issue (see: http://tinyurl.com/mmg7j5) contained a title that caught my interest: “Common blood disorder may not be linked to as many serious diseases.” The common blood disorder turns out to be MGUS.

In a nutshell, doctors have long been linking MGUS to more diseases than “just” multiple myeloma, amyloidosis and Waldenström macroglobulinemia. To my surprise, I discovered that there is a list of 75 other MGUS-associated diseases out there. 75! This list will almost certainly undergo some changes now…after the publication of the August 2009 Mayo Clinic Proceedings, which contain an interesting patient screening study declaring that the above-mentioned association is likely coincidental, in most cases, at least.

After reading the Science Daily summary, I went to have a look at the study (full study: http://tinyurl.com/lr55lc). Do you know that one of the MGUS-linked diseases is urticaria?! Eeek, just writing that word makes me itch all over!

Well, even though the full study is available online (above link), I thought I would take the time to go over a few points. Let’s see. The researchers confirmed that disorders of the bone, such as hip and vertebral fractures, osteoporosis, and hypercalcemia, are all significantly increased with MGUS, even in the absence of progression to multiple myeloma. We also confirmed known associations of MGUS with chronic inflammatory demyelinating neuropathy […] and autonomic neuropathy.

But they also found no significant association with MGUS in the 61 remaining disease diagnoses, an indication that most of these previously reported associations are either coincidental or clinically insignificant. So, in this patient population, 61 out of 75 diseases cannot be linked to MGUS. Interesting. Incidentally, see Table 2 (http://tinyurl.com/md35fy) for a complete list of diseases…you might be surprised by some of ’em…I was!

Also, have a look at Table 3 (http://tinyurl.com/mdzoqk) for a list of 20 new MGUS-associated diseases, including acute depression (!!!)…

In the Discussion part, we are also told that the frequency of osteoporosis and bone fractures is increased in patients with MGUS, independent of progression to myeloma. Eh.

Further on: The fact that we did not demonstrate a significant disease association with MGUS in such a large sample size is of major importance because it implies that these associations are likely not true associations, but rather coincidental ones. This has important therapeutic implications, because in some settings therapy has been administered to eradicate the monoclonal protein in the hopes that the associated disorder would be alleviated. Our study suggests that caution is needed.

Caution…indeed, I couldn’t agree more!

Swine flu, suppressed immunity and vitamin D

With the school year about to begin, one of the biggest news items here in Italy concerns what is commonly referred to as “swine flu” (or, more appropriately, the “novel H1N1 virus,” since this flu virus  is actually a mishmash of a few different flu strains—human, bird AND pig). How do we protect ourselves, especially those of us who are at a greater risk than the general population?

To be honest, I am not really concerned for myself, since my exposure will probably (?) be minimal compared to others…I am much more concerned for my friend Sherlock who, because of her job, has to commute by train to northern Italy at least once a week…and that is the main reason why I decided to do a bit of research and write this post.

I do believe that we can take a few extra precautions, aside from the usual, obvious ones, such as: washing our hands frequently and thoroughly, carrying a hand sterilizer around with us at all times, never touching our eyes/nose/mouth when out in public (supermarkets, etc.), avoiding folks who are coughing and sneezing, eating and sleeping well, having a healthy diet, eating lots of garlic and onions so we can keep sick people at bay, etc.

In addition to all of that, Sherlock and I are currently taking a lyophilized bacterial extract designed to stimulate our immune systems to fight against respiratory tract infections. It increases the production of our T cells and also of our IgA, IgG and IgM, so I suspect that my total IgG may be on the high side when I go in for my next set of blood tests. This is the second year I have taken these capsules, with good results, by the way.

I also believe that our daily intake of curcumin, with its antibacterial and antiviral properties, will help stave off the flu for both of us…or make it less virulent if we happen to become ill. Oh, and let’s not forget the flu vaccine that, according to today’s news report, will be available at the end of October (in Italy).

Last but not least, Sherlock and I are also taking extra vitamin D, which leads me to the main point of today’s post.

Based on epidemiological evidence and on the 1940s (!) finding that mice that receive diets low in vitamin D are more susceptible to experimental swine flu infection than those that receive adequate vitamin D (see: http://tinyurl.com/n7ytwy), the Public Health Agency of Canada is currently investigating whether or not vitamin D supplementation could help prevent the H1N1 flu. I should note that Health Canada already has an ongoing study on vitamin D and the prevention of seasonal influenza.

Another excerpt (from the above link): new research suggests that vitamin D induces the production of antimicrobial substances in the body that possess neutralizing activity against a variety of infectious agents including influenza virus.

Well, I am not going to wait for the results of the Health Canada study. It makes a lot of sense to me to take enough vitamin D to help my body fight off this and other viruses, so I have decided to increase my vitamin D supplementation a notch or two…making sure, of course, that I don’t go too near the upper tolerated limit. Too much of a good thing…as the saying goes…!

A good source of all-you-wanted-to-know-and-more information on vitamin D is the Vitamin D Council, see here: http://www.vitamindcouncil.org/ And here is the specific link to the Vitamin D Council’s Executive Director (an MD)’s responses to public questions about the H1N1 virus: http://tinyurl.com/mrssnk

Quite a bit of information on this novel virus, including symptoms and at-risk groups (people with asthma, diabetes, suppressed immune systems, heart disease, kidney disease, neurocognitive and neuromuscular disorders and pregnancy), can be found here: http://www.cdc.gov/H1N1flu/qa.htm

Hit in the stomach

I usually do not post about deaths that occur in the myeloma family…even though I am touched and saddened by each and every one. It’s all the more distressing when those who die are close correspondents of mine…or related to said correspondents, like Eric.

Well, today I am hit-in-the-stomach stunned. I found out only this morning that my blog reader/myeloma list friend Cathy died on July 7th. In April, she was hospitalized with an infection and apparently just got weaker and weaker. Cathy, my friend who loved cats…Cathy, who sent me research tips…Cathy, with her wonderful sense of humour and lovely prose…

My heart is heavy with sadness…

And Alex…oh Alex…I meant to answer his most recent e-mail as soon as we returned from our August holiday. But Alex died on August 22nd. It’s too late now.

In many ways, blogging has been a wonderful experience, an experience that will certainly continue in the years to come. I have found a purpose in life that I probably didn’t have before, I mean before my 1999 MGUS diagnosis…but these recent deaths have made me realize that my blog is also a bit of a…distraction. Doing research and answering messages takes up a huge amount of my free time. I don’t mind, of course, for obvious reasons, don’t get me wrong…but I need to do a much better job of keeping in touch with my friends, even if it means that I might be doing a little less research…a little less answering…

Never postpone to tomorrow what you can do today.

Old dog

A friend sent me this little story…I think it could have been shorter (e.g., why does the dog have to have a name?…Superfluous bit of information, in my view) and I am not sure I entirely agree with the moral, but, at any rate, it’s an enjoyable read!

A wealthy old gentleman decides to go on a hunting safari in Africa, taking his faithful, elderly dog named Killer along for the company.  

One day the old dog starts chasing rabbits and, before long, discovers that he’s lost. Wandering about, he notices a leopard heading rapidly in his direction with the intention of having lunch.

The old dog thinks, “Uh oh! I’m in deep doo-doo now!” Noticing some bones on the ground close by, he immediately settles down to chew on the bones with his back to the approaching cat. Just as the leopard is about to leap, the old dog exclaims loudly, “Boy, that was one delicious leopard! I wonder, if there are any more around here?”

Hearing this, the young leopard halts his attack in mid-strike, terrified, and he slinks away into the trees. “Whew,” says the leopard, “That was close! That old dog nearly had me!”

Meanwhile, a monkey, who had been watching the whole scene from a nearby tree, figures he can put this knowledge to good use and trade it for protection from the leopard. So off he goes, but the old dog sees him heading after the leopard with great speed, and figures that something must be up.

The monkey soon catches up with the leopard, spills the beans and strikes a deal for himself with the leopard. The young leopard is furious at being made a fool of and says, “Here, monkey, hop on my back and see what’s going to happen to that conniving canine!”  

Now the old dog sees the leopard coming with the monkey on his back and thinks, “What am I going to do now?,” but instead of running, the dog sits down with his back to his attackers, pretending he hasn’t seen them yet, and just when they get close enough to hear, the old dog says…

“Where’s that damn monkey? I sent him off an hour ago to bring me another leopard!”

Moral of this story: don’t mess with old dogs… age and skill will always overcome youth and treachery! Brilliance only comes with age and experience.

Fare thee well…

Just a lightning post to express my deep sorrow at the death of Sen. Ted Kennedy…very sad news indeed. I had the honor of meeting him in Washington, D.C., more than a couple of decades ago. A great man. This is a huge loss…not just for his family but for the entire nation…

Nauset marsh cruise

Yesterday Stefano and I finally returned to Florence. His family had planned a small gathering at his parents’ house in the Apennines (near Porretta Terme, for those who know the area) the last week in August. We had a very relaxing week—playing cards, eating wonderful food, sharing many good laughs, visiting the area (e.g., the town of Sestola where we bought delicious blueberries from Mt. Cimone and the Parco Regionale dei Sassi di Roccamalatina: http://tinyurl.com/kufy9w), enjoying the cool mountain air…in the evenings, at least (during the day, it was surprisingly hot…)…and sleeping a lot. No computer access, no blog, no e-mail. Total relaxation. Last night, when we got back to Florence, I downloaded more than one hundred messages…eeeek! Well, it will take a while to sort through the mail jumble, but I have plenty of time, as we are staying put in Florence for the foreseeable future…

Speaking of messages, Julie left a very nice comment on my August 23rd post. She forwarded bits of my summer holiday posts to a friend of hers IMG_2625who is planning a visit to Cape Cod. And that is the reason why I thought that I would add a post about our cruise around Nauset marsh…all the way up to the ocean. Julie, if your friend likes stunning views of the ocean/marsh and of shorebirds, ospreys, seals and other creatures…tell her to go on the two-hour Nauset Marsh Cruise.

You have to call the Wellfleet Bay Audubon Society (more info can be had here, see page 10 in particular: http://tinyurl.com/ljpyzn; Stefano and I went on the August 19 10 am-12 pm cruise) to find out when these marsh trips are available and make a reservation. Have a credit card handy. The Audubon Society will give you all the necessary instructions…but, in case you are not familiar with the town of Orleans, just ask for the “Goose Hummock,” which is a well-known fishing (etc.) IMG_2507supply store. You have to park your car in a small public parking lot behind the Goose Hummock, you see. My advice: get there early…we arrived about a half hour early and almost didn’t find a parking spot.

You will cruise around the marsh and all the way out to the ocean (spectacular!) aboard a pontoon boat, which is a fun, flat-bottomed boat…perfect for walking around and observing or photographing birds, scenery and houses (ah, that is the other attraction of this boat trip: you will be able to admire fabulous waterfront houses…and envy their owners!).  

We saw and photographed hundreds of birds, including egrets, at least two different types of herons and plovers, sandpipers, kingfishers, cormorants, ospreys, terns (see photo 1) and a couple of Canadian geese. IMG_2552And other birds…I don’t remember their names, sorry (see photo 2). We also came upon a group of seals lazily swimming between the marsh and the ocean.

One of the main attractions of this trip, as far as I was concerned, were the ospreys. We saw three different osprey nests (three different locations). The knowledgeable Audubon Society naturalist told us a few osprey stories. Here are a couple:

  1. An osprey couple had built their nIMG_2430est on top of a telephone pole. As the years went by, the nest got higher and higher, until one day…several distraught area residents, very protective of their osprey couple, called the Audubon Society, reporting that the enormous nest had fallen off the pole. The problem was soon solved: a nesting platform was built right next to the telephone pole. In my photo, you can see a young osprey perched on a pole close to this particular nest, crying for its mother to come and feed it. Whoah, check out those claws! 
  2. I was astonished to see some sparrows sitting on and flying around the empty-at-the-time ospreys’ IMG_2440home (if you look closely at the nest, you can make out the profile of a tiny sparrow on the top left-hand side). The naturalist explained that ospreys won’t bother the sparrows since they are exclusively fish-eaters. This happens to be THE perfect arrangement for the sparrows, whose nests, under the protection of such a large and powerful raptor, are less likely to be destroyed by egg-eating birds. Now, who says birds aren’t smart???

This will be my final post on our U.S.A. summer 2009 trip. It was a fabulous trip, but I have to say that I am glad to be home again with my parents and cats. Stefano begins work again tomorrow, and I start working next week. Fall is just around the corner, and so are my experiments…my biggest problem now is: which supplement do I try first?