Forskolin: another natural compound goes on my list of myeloma killers

Yesterday I came across a 2015 study that really caught my attention. A group of Norwegian researchers has discovered that the combination of dexamethasone with a natural compound called forskolin kills multiple myeloma cells.

They tested forskolin with other conventional myeloma drugs, too: bortezomib (Velcade), cyclophosphamide, doxorubicin, and melphalan.

And by itself.

Results in a nutshell: dead myeloma cells.  😎 

Excerpt from the abstract: “Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM.”

The researchers believe that forskolin might be able “to diminish treatment-associated side effects,” which of course would have a huge impact, obviously a very positive one!!!, on a patient’s quality of life…indeed, on the QOL of countless patients…

Of course, this is all theoretical, since the researchers used MM cell lines, not actual human beings. I checked the clinical trial website where I found only a few trials testing forskolin for various conditions, mostly eye, weight loss, and lung-related (interesting aside: there were a couple of cystic fibrosis studies there, too).

No myeloma clinical trials.

Are you surprised? I wasn’t. I mean, we know WHO finances almost all the clinical trials…and the ghastly rich and powerful pharmaceutical companies aren’t going to be interested in an affordable natural compound, are they?

No profit, no trial. It’s as simple as that.

And that is why non-toxic substances that might kill our myeloma cells without messing with our QUALITY OF LIFE are completely ignored…ignored even by our own MM foundations that should have our best interests at heart…It’s frustrating, to say the least…unbearably so, I admit, at times.

But let’s get away from negative feelings and focus instead on this potentially POSITIVE bit of news, which is that it seems we have another promising anti-myeloma tool. Yaaaaay!

Incidentally, the Norwegian study is fully available onlinegoo.gl/dRLgPg

So what exactly is forskolin? It’s a natural compound extracted from the root of an Indian plant called Coleus forskohlii. It has become popular in recent years as a weight loss supplement (the patient studies I glanced at early today, however, have mixed results). More importantly, it has been traditionally used in Ayurvedic medicine for centuries as a treatment for asthma, breathing disorders, and for general health purposes.

Contraindications. Generally speaking, forskolin is considered to be safe. However:

  • It may lower blood pressure, so definitely stay away from it if you have low blood pressure or are taking drugs for high blood pressure (beta-blockers, etc.). Of course, if you suffer from HIGH blood pressure, this might be of interest to you.
  • If you are on blood thinners such as warfarin or if you have kidney disease, forskolin is not for you.
  • It may also increase your heart rate and your levels of gastric acid.
  • There have been reports about possibly contaminated supplements in Europe.

Apart from these things, though, so far I haven’t read anything super negative about forskolin.

The big question is: will it work for myeloma patients? No idea, of course. As I mentioned, the Norwegian study used myeloma cell lines, not patients. But that hasn’t stopped me before, and it probably won’t stop me now…as long as my research keeps turning up positive information. Right now, though, it’s too hot here in Florence to think about experimenting with a new compound, which is good in the sense that it gives me time to do some further reading…

But I’m intrigued, really intrigued, and that’s a good start…

Hmmm, final (obvious!) thought: has anyone here taken this supplement? I’d love to hear from you! Thanks!

A case report: the antibiotic roxithromycin induces PR in a patient with smoldering myeloma

Well…Well…WELL!!! I’ve got a very interesting item for you today…

Many many many thanks to my blog reader Charlotte for this gem: goo.gl/hMsWov

The link will lead you to a case report about a 86-year-old patient (with IgA lambda smoldering myeloma) who went into partial remission after taking roxithromycin, an antibiotic, for just ONE MONTH. This happened last year in New Zealand.

The patient’s paraprotein, which had been increasing since he was diagnosed in 2008, dropped from 46 g/L to 20 g/L.

That’s a 57% decrease! Wowsie.

And another thing: in addition to his other markers remaining stable (calcium and creatinine, e.g.) in the four months after taking roxithromycin, his hemoglobin increased to 132…from 97. Another wowsie.

I also discovered something else: the antibiotic clarithromycin has been found to have anti-myeloma activity BUT only in association with other drugs (dexamethasone, etc.). That’s the difference between the two antibiotics, since roxithromycin appears to have “significant single-agent anti-myeloma activity.” That is, it goes after myeloma all by itself…

I’m not a big fan of antibiotics, that’s for sure (although when you need ’em, you need ’em!!!), but this case report has certainly given me food for thought…

A lot of food for thought…

 

A new commission looks into the adverse effects of blood cancer treatments

This morning I read an IMPORTANT Science Daily article on how the adverse effects, tolerability, and toxicities of conventional treatments for blood cancers (including myeloma, of course) have not been reported/disclosed as well as they should have been, to put it mildly. See: goo.gl/ou9CNg

Well, this may change soon enough: a new commission set up by The Lancet Haematology has been looking into these adverse effects and toxicities, considering in particular the long-term, chronic effects that don’t go away even after the completion of treatment, such as neuropathy, which can be crippling.

Quality of life has always been a big concern of mine, and I always look for adverse effects and toxicities whenever I read studies about patients and conventional treatments. Very rarely, however, are adverse effects mentioned…The first study that comes to mind is the Spanish SMM patient-chemo study, where there was no information on how the early treatment of SMM patients affected their daily lives. And yet their lives must have been affected, at least in some ways…

Excerpt from the SD article: “In particular, the toxicity over time and tolerability to the patient of new chronic or continuously administered therapies are not well defined, and are poorly captured by existing reporting mechanisms.

Well, the important thing is that FINALLY (about time!!!) there is a commission looking into this lesser-disclosed (to say the least) part of conventional treatments. This is very good news.

We, the patients, need to be INFORMED about any and all potential problems, both short-term and long-term…

Or, at least, that is MY opinion! As usual!!! 🙂

Researchers test curcumin in new bone-building study

After enhancing the bioavailability of curcumin using polymers, a group of Washington State University researchers proved that curcumin can increase bone growth by between 30% and 45%  in a matter of weeks: “The presence of curcumin in TCP results in enhanced bone formation after 6 weeks.” (Quoted from the abstract.)

The researchers are currently testing other natural extracts as well, namely “aloe vera, saffron, Vitamin D, garlic, oregano and ginger [… ] that might help with bone disorders, including those that encourage bone growth or that have anti-inflammatory, infection control, or anti-cancer properties.” (Quoted from Science Daily, see link below.)

The bone-forming qualities of curcumin are nothing new to us (I’ve written a number of posts on this topic), but it’s always good to learn that researchers are looking for, and apparently FINDING, new ways to make curcumin more bioavailable, especially if it has to do with our precious bones!

Note: this study was carried out on 3D-printed, ceramic bone scaffolds, not on human beings. So there is still a long way to go. Still, it is encouraging to have one more study prove the importance of curcumin for bone health and growth…

Curcumin forever!

Here’s the very interesting write-up in Science Daily (easy to read, to boot): goo.gl/MRxtK2 There is a link to the study’s abstract there, for those who want to know more.

Happy reading! 🙂

Quick post

Wow, it’s been a long time since I last published a post. Everything is fine, more or less…This has just been a super busy period…

In a nutshell: our two mischievous kittens (see the awful cellphone photo on the right) were spayed a couple of weeks ago after the scare with Pandora’s heart turned out to be just that. I mean, it was just a scare, luckily!!! They are doing just fine and are as mischievous as ever.

Then Stefano and I spent four days at a cousin’s wedding in Avellino, a town near Naples, then there were a million things to do once we got back to Florence, teaching English blablabla…then Stefano came down with a cold, which developed into bronchitis, which he passed on to me this past weekend. And so I’ve been coughing up a storm since Sunday (oh how I hate THE cough!!!)…But I’ll be fine, no worries…I feel much better today. I’ve been taking antibiotics, probiotics, the usual curcumin, Reishi extract, and the most important thing: an expectorant cough syrup (yeah, gross, I know…but essential in these cases). Bronchitis in June…makes no sense. There you go.

And then…also…eh…last week a friend’s husband, who’d had myeloma for 12 years, died…He was just a few years older than I am…I’ve been in touch with his wife for years…for years…so sad.

Crappy, crappy myeloma, grrrrr!!!  👿

Anyway, lots going on, as you can see. But now I have to get off the computer, so I hope everyone is fine and dandy. Ciao for now!

Two gadolinium-based contrast agents are banned in Italy

Wellwellwellwellwell! WELL!

I just read a bit of welcome (or, wellcome!) news in Italian. If you understand Italian, here’s the link: goo.gl/JYN8ec. In a nutshell, beginning today, yes, TODAY!, two contrast agents used in MRIs have been banned in ITALY. And, quelle surprise (not), they are gadolinium-based.

Remember the study that came out some years ago about how much myeloma cells simply LOVED gadolinium, and proliferated at mad rates when placed in it? If not, just do a search of my blog for “gadolinium.” Gadolinium can also have a bunch of not-very-nice side effects…

The reason for this ban isn’t, however, because of that important gadolinium-myeloma study. No, what’s happening today in Italy is mostly a precautionary measure, based on the July 2017 recommendations of the EMA, the European Medicines Agency, which in turn are based (!) on the findings of its Pharmacovigilance Risk Assessment Committee, which is Europe’s equivalent to the U.S. FDA. Basically, small quantities of gadolinium have been shown to accumulate in the brain, and there is no way of proving that those quantities do not cause any damage in the long term.

Hence the ban.

Does that mean that gadolinium has been completely banned? Unfortunately not.

In some cases–when there is no other way to reach a diagnosis, e.g.–the smallest dose possible will be used. But there will be no more widespread use of this crap. Oh sorry, did I say “crap”? Oh dear, so I did. 😉

Another thing: the gadolinium-based contrast agents gadoxetic acid and gadobenic acid will continue to be used in liver scans.

But that is IT. Gadolinium is on its way out (at least, that’s what I hope!).

We need to focus on finding non-toxic or at least not-so-toxic contrast agents. There must be another way to do this…there must be…

Ah, speaking of which, I just read about potentially safer manganese-based contrast agents in an article titled “U.S. patients left fending for themselves with gadolinium safety risks”: goo.gl/zCz5gM

And this is where I am going to stop today, with the hope that a non-toxic contrast agent can be found…

P.S. I’ve been having difficulty accessing the Internet in the past few days…It’s on, then off, then on again…a real drag. I want to publish this post before I lose Internet again, so I’m not going to reread it, as I usually do…pazienza!

Off I go…Need to feed the cats and have lunch! Ciao! 🙂

Andrographolide and parthenolide kill myeloma stem cells

My andrographolide-researching blog reader also sent me the link to a 2011 U.S. study on the effects of parthenolide (remember PTH? Remember DMAPT? Yeah, I haven’t written about it in a long time…making mental notes right now…) and andrographolide on myeloma stem cells: goo.gl/3e6Nk5

That’s right…on MYELOMA STEM CELLS.

Problem: only the abstract is available for free online. With the help of a fab friend, however, I was able to read the full study, but I have to be careful about copyright issues, even though it irks me that you have to pay for studies that could be of vital importance to us. Of course, I DO understand that journals need to survive. And so…well, let’s have a look, without going into too much detail. Compromises…

Incidentally, this is the first study discussing “a natural product with anti-CSC activity in myeloma” (CSC = cancer stem cell).

As we all know, the main problem with myeloma is RELAPSE. Relapse is caused by the tough myeloma stem cells, the cells that can clone themselves, the really bad thugs that escape being killed by chemotherapy. The chemo drugs used in myeloma target the general plasma cell population, that is, the cells that cannot reproduce themselves, BUT they are NOT able to eliminate our myeloma stem cells. So no matter how many chemo bombs we throw at our myeloma, there will always be a handful of nasty ruffians in hiding, ready to come out and start proliferating again at some point.

This study shows that parthenolide AND andrographolide do just that: they go after the ruffians. The abstract calls them two “potent anti-MM-CSC agents.”

Potent…I like that!

Okay, I’m going to see if I can extract some gems from the full study.

As we’ve seen, it’s not enough to target the circulating plasma cells. If we want to get rid of the myeloma weed, we must go after the stem cells, the “clone troopers” (Star Wars, anyone? 😉 No, I’m not really a fan, but I do remember that expression…). The only way to prevent relapses is to kill the cloners!

Parthenolide is the first extract to be discussed. In addition to being a powerful NF-kappaB inhibitor, parthenolide (PTH from now on) kills the stem cells of myeloma and of acute myelogenous leukemia, without killing the normal hematopoietic cells, the good guys, which produce red/white blood cells and platelets. One big problem has been PTH’s has low solubility in water (but remember DMAPT? It’s water soluble… but these researchers don’t mention DMAPT, except in their References…anyway…).

Andrographolide (AGR from now on) hasn’t been studied as much as PTH. However, it’s more soluble in water compared to PTH. That is very good news…

The researchers point out that melphalan and bortezomib “are not curative” (their words, not mine), because they don’t target the MM stem cells.

But, they add, that’s what PTH and AGR do…

One of the coolest things about this study, IMO, is that the researchers used a 3-D tissue culture of rBM, which is basically a reconstruction of a bone marrow microenvironment (rBM stands for reconstructed bone marrow). They also used 2-D cell cultures. They were able to confirm that the main target of PTH and AGR were the myeloma stem cells.

Clearly, more research is needed…more testing…but I’d say that this study shows how promising these two extracts are. We need to rip out the myeloma weeds…without harming ourselves in the process…

Testing promising natural extracts is a step in the right direction.

Are our official myeloma organizations going to do something about this very important study??? C’mon!!!!!!

Out in the cold

I just read an article mainly about the cost of Revlimid in the U.S.A. and the “games” that Celgene, the maker of Revlimid, has been playing in order to prevent it from becoming a generic drug.

The article tells the story of Pam Holt, a myeloma patient and retired educator, who pays $640 a month in order to take Revlimid: http://goo.gl/LHa5Jn

Having myeloma is hard enough, but being forced to go into debt in order to have conventional treatments is simply OUTRAGEOUS.

The greed of these big drug companies has to be stopped…

I consider myself extremely lucky to live in a country (Italy) where nobody has to pay a cent for their conventional treatments. It should be the same in every country.

Does myeloma run in the family?

Ever since I began doing research on myeloma, one of my certainties–although with something like myeloma you can never be absolutely certain!!!–has been that myeloma is NOT a hereditary disease. Yes, of course, I’ve read about a few patients who had relatives with myeloma, but…only a few.

If you do an online search, you will find that not much is known about the causes of myeloma. A few known ones are things such as pesticide exposure, past exposure to radiation, genetic changes that turn our plasma cells into MM cells…stuff like that. The family connection seems to be a minor one…

Today, however, I read a Science Daily article that suggested otherwise. As you can see for yourself (goo.gl/jPgDtS), the article begins like this: “Researchers have identified two gene regions that contribute to multiple myeloma, an inherited cancer…”

SAY WHAAAAAT??? MYELOMA…AN INHERITED CANCER?

The Science Daily article picked this up from a newly published gene mapping study that I won’t even try to read today (my brain is still reeling from that “inherited” business). If you’re interested and find technical jargon as fascinating as my kittens find me doing practically anything 😉 , go right ahead and have a look: goo.gl/bTgGmW

Still stunned, I immediately began digging and found a few relatively new studies on the apparent inheritance factor. A 2013 “Leukemia” study uses the expressions “familial clustering” and “genetic predisposition” in its abstract, but the full study isn’t available for free online, so I wasn’t able to check it out. For what it’s worth, here’s the link (to the abstract): goo.gl/kr2Fq2

According to another study published in 2016 (see goo.gl/nNqqJh), full study available online, “Results from this pooled analysis provide compelling evidence to support hypotheses that genetic inheritance plays a role in the aetiology of MM.” The risk is greater if you have a first-degree relative with myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, or leukaemia.

But is that enough evidence? I mean, can we really define myeloma as an “inherited cancer”?

Of one thing I am certain: nobody in my family has MGUS, let alone MM. I’m the first (and last, since I don’t have any children, apart from the marvelous furry ones, of course!). Besides, based on my most recent readings, I am 100% positive that EBV started my myeloma.

I think there are too many potential causes out there, there’s too much we just don’t know (for example, the bone marrow microenvironment wasn’t even considered to be an important player in myeloma until a decade ago), for us to be able to define myeloma as a hereditary type of cancer. Or…am I wrong?

I’d be really interested to know how many of you have myeloma (or leukemia/lymphoma) in the family…

“The bone-marrow niche in MDS and MGUS: implications for AML and MM.” Part 2.

Back to the Dana-Farber study that I wrote about a couple of days ago.

The section titled “Therapeutic opportunities” is interesting. How to prevent progression, that is. As you can imagine, the chef’s daily special consists only of conventional treatments. For example, the authors make a reference to the Spanish study (Mateos et al) that I have repeatedly condemned here on the blog. The Spanish researchers–some with strong ties to the big pharmaceutical companies (hello???)–tested lenalidomide and dexamethasone on a group of SMM patients. The study claims to have prolonged progression-free survival and even overall survival in those patients…without ever taking into consideration QUALITY OF LIFE. Sorry, but I have no patience for statistical studies that play with people’s lives…

That said, the trend toward early intervention is clearly taking off, as the Dana-Farber study points out. Very unfortunate, IMO.

And there is no way to stop it, except that we, the patients, can say just say NO. Of course, if you have CRAB symptoms, that’s another matter. But, in the absence of the CRABs, WHY TAKE THE CHANCE OF WORSENING YOUR QUALITY OF LIFE?

Makes zero sense.

And there’s another thing that bothers me: where’s the proof that the overall survival of someone with SMM was extended thanks to these conventional treatments? Do the Spanish researchers have crystal balls that give them the exact times of death for their patients, both with AND without treatment? Oh, right, no, that’s what their STATISTICS tell them. Based on the patients’ “high-risk” data (see yesterday’s post).

I’m not saying that statistics can’t be useful in certain circumstances, mind you. But in these cases, when someone with no CRABs is deciding on whether to agree to early treatment, or not!, they can be harmful. If I had agreed to begin conventional treatments in 2005, I don’t know where I would be today (according to my former hematologist, I’d be dead…would have died in 2010…didn’t happen, OBVIOUSLY!!!…I’m still here, still splendid 😉 , still no CRABs, still no conventional treatments…).

Sorry for the rant. Okay, let’s calm down and try to understand the rationale of early intervention from the Dana-Farber study perspective. The researchers say that if the number of osteoblasts (bone-forming cells) can be increased in the early stages of myeloma, myeloma cells cannot proliferate. That’s good to know. There are non-toxic ways to do that, btw, but let’s keep to the study…

Mice that were injected with nanoparticles loaded with bortezomib before being contaminated with MM cells lived longer than non-injected mice. The researchers give another example in which early treatment of an antiangiogenic antibody was used on mice. Okay, but we’re talking about mouse models here. The reality, as the researchers themselves admit at the end of this paragraph, is that “…the use of antiangiogenic agents other than thalidomide and other immunomodulatory agents has not been shown to be successful in patients with MM.”

Not successful in patients.

So much for that.

Then there’s immunotherapy, which we have heard and read a lot about in the last few years. You may have heard about the anti-CD38 antibody known as daratumumab, which activates the immune system.

Anyway, it’s in this paragraph that I found a remarkable admission.

But first, let me say that ever since I joined online myeloma support groups, one of the key issues we discussed was what how to deal with our immune system. Should we stimulate it, thereby possibly stimulating our myeloma cells, too? Or should we avoid anything that stimulates the immune system? The consensus usually drifted toward the former approach. I wrote a post about this in 2013: http://margaret.healthblogs.org/2013/10/20/long-term-survival-in-myeloma-is-finally-linked-to-a-robust-immune-system-and-my-new-discovery/

I’ve had mixed feelings about it throughout the years, but my gut has always told me that it makes no sense to keep our immune system weak.

And here, in this paragraph, I finally have my answer (vindication!!!): “Indeed, trials involving these antibodies provide the first proof of concept that activation of the immune system has therapeutic benefits in patients with MM.”

After years of not knowing what to do, we finally know that having a strong immune system is GOOD.

Quelle surprise…not.