Venaria Reale

May 25, 2009 / / 3 Comments

I have to admit that I was a bit disappointed in the ancient Egyptian exhibition hosted at Reggia Venaria…yes, there were some magnificent colossal statues, and the one in the last room was splendid…but I had expected to be absolutely floored by the reproduction of the underwater environment…and…well, that just didn’t happen. The “underwater” part of the exhibit consisted mainly of a series of darkened rooms…one in particular was a dark narrow hallway displaying artefacts behind small glass “portholes” positioned at various heights. Under normal circumstances, bending over to peer inside a “porthole” would not have been a problem…but on Saturday afternoon the place was crowded with hot and tired tourists wandering around aimlessly in the very stuffy darkness. I had to be careful about not bumping into them. That was a rather unpleasant experience, yes, especially whenever I heard someone cough nearby (YIKES!). I don’t suffer from claustrophobia, but if I did…well, I’d have scampered out of there like a rabbit fleeing from hungry lions!

In conclusion, I just didn’t enjoy the exhibit as much as I thought I would (my B.A. is in Social Anthropology, you see, and at one point in my life I really really wanted to be an archaeologist…archaeology remains one of my passions). To be fair, thought, there were some stunning pieces in the exhibition…so in the end it was probably worth the nine-hour round trip. I just wish we hadn’t been so oxygen-deprived in the exhibit, and that my expectations had been a bit lower.

After the exhibit, we went through the royal palace. Well, after seeing what is considered to be one of the most splendid examples of Baroque architecture (certainly in Italy), it’s clear to me that the only thing I like about that entire period is the music: Bach, Vivaldi, Handel, Purcell etc. Nope, Baroque architecture is definitely not my cup of tea…but, certainly, very grand!

The palace gardens. Ah, again, a bit of a disappointment. But it is also true that Saturday afternoon was very very hot and humid, so wandering through a garden offering very little shade certainly didn’t add to our enjoyment. I did think the rose bush garden was lovely, though. But why were all the roses white? I would have preferred to have seen rose bushes in different colours…

Oh bother, today I must seem like Mary Mary Quite Contrary…yet I am actually very happy and excited, since my parents, who are still in the U.S. right now, are arriving tomorrow afternoon in Florence. Tomorrow morning I am going to work as usual but will leave in time to meet their flight…at 2 PM. Unfortunately for them, Florence is on red alert right now…one of the hottest cities in Italy (quelle surprise!). An unusual heat wave for the month of May…luckily the heat is supposed to end a few days from now, and temperatures are supposed to go back to normal. I really hope so. I am about to melt!

Moringa oleifera and myeloma

May 18, 2009 / / 7 Comments

Thanks to a fellow blogger, Dave (whose two-year-old son Jaymun has been battling AML since birth; the link to his website, “Jaymun’s Journey,” is on the right-hand side of this page), I learned of a new plant with amazing anticancer (etc.) powers: Moringa oleifera.

This morning, in fact, I read Dave’s recent report on a group of creative and dedicated Wisconsin high school students who tested a tropical plant extract on a group of mice with cancer. The mice not only survived but also appeared to have lost their tumors, whereas all the ones in the control group died. The students also administered this plant extract to healthy mice that became more active and appeared younger. More details on this fascinating story can be found here: http://tinyurl.com/p8g7yf

Moringa oleifera is a very nutritious tree…I mean, yes, you can actually EAT it. I read that its leaves contain more protein than yoghurt (!)…and also calcium, iron, vitamin Bs and so on. For a description of the Moringa oleifera tree, see: http://en.wikipedia.org/wiki/Moringa_oleifera Here I read that parts of the tree are used as an antiseptic and in treating rheumatism, venomous bites (!) and other conditions. Interesting…but does it affect myeloma?

Wellwellwell, after a very quick Google search, I found a 2007 study according to which Moringa oleifera is indeed strongly cytotoxic to myeloma cells. “Oh, this is good, this is very good!,” I thought. I then checked PubMed where I found 124 studies dealing with this tree and many of its amazing properties. Today, however, I barely have enough time to take a quick look at the 2007 myeloma study. As follows.

The study (full study: http://tinyurl.com/oaeo4s) tells us that Moringa oleifera is a multipurpose tree widely distributed in Asia and commonly used in Indian traditional medicine. The leaves of this tree were used in folk remedies for tumors and as a food source for humans (and, I read elsewhere, for animals, too).

Why am I not surprised to read that this tree yields substances that are antioxidant, anti-bacterial, fungicidal, hypocholesterolemic and anti-diabetic? Familiar story, eh. In any case, the researchers tested both Moringa oleifera and Vinca rosea leaf extracts (the drugs vincristine and vinblastin derive from the latter, btw) on myeloma cells. They found that the Moringa extract had much stronger anti-myeloma effects than the Vinca one. Well, how about that?

More testing is needed, of course, but this preliminary data sounds very very good to me…enough to say that another promising substance has joined my rather…substantial, by now, list of anti-myeloma non toxic plant extracts…yay! Oh bother, my time has run out…I really must dash off now to prepare my classes for tomorrow. Ciaooo!

P.S. yes, my blog banner is a photo of Piazza del Campo, Siena. Bravi!

Phase I trial of feverfew in cancer patients

May 16, 2009 / / 9 Comments

Those of you that who been following my blog in recent times know that I have been through a rather difficult period, emotionally speaking (in particular, the death of a close relative in Stefano’s family) and am only now getting my brain back on track…beginning to read studies again and so on. I have dozens of fascinating studies and Science Daily newsletters piled up on my desktop…plus interesting material and links that many of you have been sending to me. I should be finished by the year 2195…

Speaking of blog readers: Barry, I tried to send you TAB’s report, but I keep getting an “impossible-to-be-delivered” message. Sorry. I tried twice…failure both times. This happens now and again: I reply to a blog reader’s question, but my message doesn’t go through. So, if you have asked me a question and haven’t heard back from me, it may not be my fault (how’s that for a good excuse? hehe). Seriously, though, try writing to me again, using a different e-mail address if possible. Thanks!

Let’s get to today’s topic. In one of my posts on feverfew/parthenolide (PTL)/DMAPT, I mentioned en passant a 2004 Phase I feverfew trial…but I recall that I only glanced at the abstract and, back then, didn’t have access to the full study. Then I must have forgotten about it. Well, it just so happened that last week Sherlock (sei fantastica!) found and sent me a bunch of full studies on various topics, including, yippee, the 2004 feverfew trial study (abstract: http://tinyurl.com/qd7l85). Super!

Oh, before discussing the full study, I just wanted to say two more things. 1. I have planted two more feverfew plants in my front yard. The one that I planted last year barely made it through the summer and then died, much to my sorrow. It was my own bloody fault. It was a hot summer so I kept watering it…and I probably ended up drowning the poor thing. This just goes to show that too much love and attention and may not necessarily be a good thing. Anyway, this year I will do my best not to over-water the two plants that Stefano’s aunt sent to us from southern Italy. Fingers crossed. Actually, thus far they are doing fine…indeed, they are about to flower; as soon as that happens, I will post some photos.

2. In November 2008, soon after taking my first feverfew pill (not the Tanacet brand used in the 2004 clinical trial, by the way, but another brand containing a slightly higher PTL percentage), I felt a surge of heat on my upper lip. I checked in the mirror, and there it was: a small but rather angry cold sore. Stefano accompanied me to a pharmacy to buy some zovirax cream that I dabbed on the spot. The following day it had vanished. Other than that minor incident, I didn’t have any particular problems with feverfew.

Okay, now for the study. The abstract, which you can go read on your own, explains what feverfew is, gives the basic info about the trial and so on. As many as 4 mg of feverfew were given to a small group of cancer patients who experienced no significant toxicity. Interestingly, the maximum tolerated dose was not reached. I had to read the entire study to find out why.

On the down side, even at the highest dose—4 mg—there was no detectable concentration in the plasma. That means that feverfew is probably poorly bioavailable, as the researchers also suggest further on in the study. But, because of my initial reaction to the feverfew pill (the cold sore, I mean), I wonder if, like curcumin, feverfew might work on different areas in the body…other than the bloodstream, that is. These are the ramblings of a non-scientific mind, of course. Okay, let’s take a look at the full study.

The first paragraph makes the point that many chemo drugs derive from plant extracts: The taxanes, paclitaxel and docetaxel, are very important anti-cancer drugs derived from the yew plant family. Then we read a list of parthenolide’s properties…the main ones are potent in vitro anticancer and antiangiogenic properties, inhibition of NF-kB, IL-6, IL-8 and drug resistance.

The purpose of this clinical trial was to see if PTL would show up in cancer patients’ blood. It was administered daily for 28 days. Subsequent 28-day cycles were administered with an intervening break. No more than 4 mg/day were given because of drug supply issues…and financial considerations. Aha, that explains why the maximum tolerated dose wasn’t reached in this trial.

The patients took feverfew capsules (brand: Tanacet) containing 500 mcg of PTL, in the morning on an empty stomach (ahhh, how I loved all these details!). They were instructed not to eat for 1 hour after ingestion. More details: In cycle 1, blood samples were drawn on day 1 and 29 in the following fashion: pretreatment, and then 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 12, and 24 hours after the ingestion of the capsules.

Patient information: Twelve patients with advanced solid tumors were treated with feverfew. The median age was 73 years (range 48 to 80). There were 11 men and 1 women enrolled. The cancers treated included eleven prostate and one breast and all patients had metastatic disease and had received prior therapy.

Problems. Even though the patients experienced no significant toxicities, the trial was stopped at the dose level of 4 mg daily once it was determined that no parthenolide was identified in the plasma of any of the patients. By the way, side effects included: fever, gastrointestinal side effects, chills, fatigue, and blurred vision. The blurred vision and fever were experienced by a diabetic patient, therefore causes other than the feverfew were considered more likely.

The ominous statement, “No patients responded to therapy,” certainly did not bode well for my own recent experiment with feverfew. You see, I took one 600 mcg PTL pill, that is, quite a bit less than the 4 mg/day dose…it seems that I should have been taking 5 or 6 pills. Well, live and learn. But the researchers had also written that, while some patients requested to leave the study and others left because of disease progression, some (no details given) had responding or stable disease, with no appearance of new lesions, and were thus allowed to stay in the study for six cycles. Furthermore, If a patient had evidence of continued response after 6 cycles, treatment was to be continued for two more cycles beyond the best response. Okay, there is no question that this part is more than a tad confusing. Perhaps I should write directly to the researchers. In any case, as far as my own experience is concerned, I have been taking feverfew since November 2008…so perhaps, uhm, the temporal effect added to my wishful thinking and positive attitude will make a difference. Realistically, though, I won’t be surprised if my next test results don’t change one whit.

Toward the end of the study, the researchers state that their efforts will now focus on purifying parthenolide and identifying causes for the inability to deliver systemic levels with low doses such as 4 mg of parthenolide per day. And, further on, The data from our trial supports the need to purify parthenolide and administer higher doses. I wish them success!

Another anti-myeloma compound: pristimerin

May 15, 2009 / / 1 Comment

Remember my post/page on celastrol (from the thunder of god vine)? Well, for a memory refresher, you can scroll down my Pages to the one titled: Other anti-myeloma/cancer substances.

At any rate, a few weeks ago, looking through the table of contents for the April 23 edition of “Blood,” I came across a study discussing a related compound (Sherlock, grazieee!, sent me the full study): pristimerin, a naturally-occuring substance that has strong anti-myeloma activity. See abstract: http://tinyurl.com/dbr36b

Since one of the proliferation factors involved in myeloma is cyclin D, a group of researchers from different cancer institutions conducted high-throughput chemical library screens for compounds that induce suppression of cyclin D2 promoter transcription. The top-ranked compound was a natural triterpenoid, pristimerin.

A natural triter…huh? No worries, I looked it up. Triterpenoids (hehe, try saying “triterpenoid” ten times FAST!) are biologically active, anti-inflammatory, anticancer and antioxidant compounds extracted from many plants, e.g. from the Celastrus and Maytenus species. Remember my posts/pages on glycyrrhizin, ursolic acid, betulinic acid, celastrol and oleanolic acid? Well, these substances are triterthingies, too. Okay, with that matter cleared up, let’s give this thing a go.

From the abstract we learn that pristimerin strongly inhibits proteasomes. (Ah, just like bortezomib and, ta-da!, curcumin.) In fact, I found a 2008 study on that very topic: http://tinyurl.com/pct6y7 The abstract tells us that pristimerin has been used for ages in folk medicine as an anti-inflammatory remedy. Now, where have I heard THAT before…? Anyway, in addition to killing breast cancer cells, pristimerin also targets proteasomes in prostate cancer cells. Well, well…

Okay, back to the April 2009 “Blood” study. Interesting titbit: pristimerin’s anti-proteasome activity occurs even at low concentrations. Furthermore, this substance inhibits our old enemy, hyperactive NF-kappaB, as well as cyclin D expression. In fact, it does such a good inhibiting job that the researchers make the following statement: As a consequence, pristimerin induces selective myeloma cell apoptosis in vitro and in vivo with greater potency than that described for other antineoplastic triterpenoids such as celastrol or CDDO, which are currently in clinical trials. Not bad, eh…

Okay, let’s get to the good stuff. In lab tests, pristimerin caused substantial suppression of all the cyclin D proteins. Even myeloma-friendly cytokines such as IL-6 could not protect myeloma cells from certain death. Hah!

Pristimerin was tested in vivo, too…specifically, on…gee, one guess!…nude mice with implanted plasmacytomas. The first experiment showed that high doses of pristimerin were too toxic…the mice had to be put out of their misery. So the researchers developed a liposomal formulation, which turned out to be less toxic and better tolerated in a second mice-based experiment. Result: Statistically significant tumor growth inhibition occurred at pristimerin doses of 2 to 3 mg/kg intravenously twice weekly, compared with vehicle-treated mice.

Pristimerin also worked in synergy with bortezomib. The two substances alone were less effective than when combined.

In the study’s Discussion, the researchers declare that pristimerin possesses substantial antimyeloma cytotoxic activity […] with a potency more than 10-fold that of CDDO or betulinic acid for solid organ malignancies, and more than 2- to 3-fold that of CDDO for multiple myeloma,39 and that pristimerin is synergistically cytotoxic with bortezomib, perhaps the most active antimyeloma agent in the clinic today.

Further on, they add that Uniquely, we find that pristimerin induces significant proteasome inhibition, which likely contributes to both its inhibition of NF-kB pathway signaling and specific cytotoxicity in myeloma. To our knowledge, no other triterpenoid has been demonstrated to inhibit proteosome function, although such activity could perhaps account for some of the activities of cytotoxic triterpenoids. Using in vitro and in vivo studies, we demonstrate that pristimerin causes selective antimyeloma cytotoxicity, within a therapeutic window, identifying it as a lead compound for the development of enhanced triterpenoid-derived anticancer pharmaceuticals.

They also raise the possibility that pristimerin might be able to overcome myeloma’s well-known ability to become resistant to conventional treatments.

Well, this is simply an introductory report on yet another promising anti-myeloma substance extracted from plants. Clearly, more research and testing are needed…and no, I am not ready to fly to China, hunt down and munch on the roots of Celastrus hypoleucus, a pristimerin-containing plant…nope, not yet!

A few links to pristimerin studies

1. “Antiproliferative activity of pristimerin isolated from Maytenus ilicifolia (Celastraceae) in human HL-60 cells,” 2008: http://tinyurl.com/rbukj5

2. Triterpenoids and doxorubicin, 2006: http://tinyurl.com/qzahub

3. Anti-cytomegalovirus activity of pristimerin, 2007: http://tinyurl.com/q83kmy

4. Antifungal properties of pristimerin and celastrol, 2005: http://tinyurl.com/o99rrg

5. More information on triterpenoids, 1986: http://tinyurl.com/db8cde