During a visit to the mental asylum, a visitor asked the Director: “How do you determine if a patient should be institutionalized?”

 

Well,” said the Director, “we fill up a bathtub, then we offer a teaspoon, a teacup and a bucket to the patient and ask him or her to empty the bathtub.”

 

“Oh, I understand,” said the visitor. “a normal person would use the bucket because it’s bigger than the spoon or the teacup.”

 

“No,” said the Director, “a normal person would pull the plug. Do you want a bed near the window?”

 

(I bet you chose the bucket, didn’t you? Hehe…by the way, thanks so much, Beth, for sending this to me! My parents and I howled for at least five minutes!)

My parents arrived safe and sound earlier this afternoon. After the long flight from Boston to Florence (via Zurich), though, they needed a rest. The cats are resting with them (sooo cute!), so I thought I would quickly check my messages and write a brief post.

 

In the June 15 “Blood” Table of Contents I came across a study on parthenolide by Craig Jordan, Monica Guzman and the University of Rochester/University of Pennsylvania team. As you can read in the abstract (see: http://tinyurl.com/4v2re6), the team discovered not one but two (!) new agents, celastrol and 4-hydroxy-2-nonenal, that effectively eradicate AML at the bulk, progenitor, and stem cell level. Wowie!

I don’t have a lot of time now, and, besides, I don’t have access (yet) to the full study, but just for the heck of it I quickly looked up celastrol, which turns out to be an active antioxidant compound extracted from the root bark of a Chinese perennial plant called “Thunder of God Vine.” (Don’t you love that name?)

You can read a bit more about it in this 2006 study published in “Cancer Research”: http://tinyurl.com/3l7js6 But, in a nutshell, it has been used for a long time in traditional Chinese medicine to treat inflammatory conditions. It is a proteasome inhibitor (like Velcade) but with no toxic side effects. As far as nude mice are concerned, at any rate! Interesting titbit: I read that its leaves and flowers are highly toxic. I suppose that rules out any possibility of making any thunderous cancer-stem-cell-killing tea, huh?

Well, still, a very exciting bit of news. And my parents are here to share it with me.  I have quite a bit of research in my future, that much is clear!

My parents are arriving here tomorrow from the U.S. (yippee!), so, as you can imagine, I am busier than busy these days. No time to post, answer e-mails, nada de nada…please be patient. Things will get back to normal in a few days, once my parents have settled in and so on. At that point I will try to answer at least some of the messages I have received and do some research.

 

I have received some very interesting comments recently, so please check them out if, like moi!, you like to read blog comments (the easiest way to do that would be to scroll down this page all the way to the bottom and, on the right, you will find the heading “Recent Comments“ that lists the most recent comments).

 

For instance, my blog reader Roberto, who has MALT lymphoma, has a few suggestions on how to use feverfew. The important thing, he writes, is to use parts of the whole plant. I think I may try doing just that this summer. My parents are bringing me a parthenolide supplement, but the percentage of PTL is so low that I am not sure what good it will do, if any. If at the same time I drink feverfew tea made with my own feverfew plant, though…wouldn’t that give my myeloma cells a double whammy? (Wishful thinking!)

 

By the way, to answer Munjid’s question, feverfew is indeed related to chamomile. One of its earliest scientific names was Matricaria parthenoides, and the Latin name for chamomile is Matricaria recutita. They both belong to the chrysanthemum family (fancy that), from what I read. They look similar, but there are differences if you look closely. Stefano’s aunt explained to me the other day that feverfew, for instance, lacks chamomile’s protruding central disk (its centre is flat).

 

A blog reader privately sent me a question concerning white cell count and creatinine, but I seem to have deleted or lost that message by mistake. If you read this, please drop me a note again. Very sorry about that!

 

Ok, I must be off, it’s getting late!

Tantissimi auguri di buon compleanno all’uomo straordinario che ho avuto la grande fortuna di incontrare, che dopo tanti anni è ancora capace di sorprendermi e di conquistarmi e che mi ha portato a vedere i pulcinella di mare (soprattutto! ). Lo sai che non sono per niente brava con le smancerie e così, oggi che compi 45 anni, ti dico semplicemente che…

 

ti amo (anche più di quanto non ami i nostri gatti!)!

As some of you know, I teach English in a company based in Florence, Italy. My students, divided into four small groups (different levels of English), frequently come up with the funniest stuff. In fact, I should really write a book about this experience…hmmm…

At any rate, the other day I was going over how we say numbers in English with my pre-intermediate class, a group of three cheerful chirpy women who are always ready for a good laugh. At one point we got to the number “one hundred thousand.” In Italian, one hundred is cento and one thousand is mille. One hundred thousand is the combination of those two numbers = centomila. As it is in English.

 

I asked M., the company accountant, if she would read that number in English, but she looked at me blankly and groaned: “ora non mi viene” (=“I can’t remember how to say it now”).

 

I asked: “Okay, let’s see, what’s that number in Italian?”

 

She answered straight away: “Centomila.”

 

“Well, it’s the same in English!,” I said encouragingly.

 

She smothered a grin and answered, “Ah, then: centomila!”

An aunt and uncle of Stefano’s spent the Xmas 2007 holiday with us. One day I told Stefano’s plant-loving aunt about parthenolide, or PTL, the active myeloma-cell-killing ingredient in the feverfew plant. She recognized the Latin name of feverfew (Tanacetum parthenium) and gasped: “But my mother has this plant growing WILD in her back yard!” Oh, you can imagine my delight at this bit of news! She promised to dig up and send me a bit of this plant as soon as spring arrived. So I now have a pretty little feverfew plant in my front yard (see the photo I took this morning). Now, I am not sure what I will be doing with it (preparing teas, perhaps? The highest concentrations of PTL, I read, are in the flowers and fruit of feverfew) but at the very least I am sure it will bring me good luck.

 

I used this little story and my photo as an introduction to today’s post about a recent U.S. study on the anti-myeloma effects of partenolide. I have already posted about two previous studies on the same topic–one Chinese, the other Japanese. For background info, please see my Page on parthenolide/DMAPT.

 

A blogging friend (thank you!!!) sent me the full text of this Indiana University School of Medicine study published in Clinical Cancer Research on March 15th 2008. In the abstract (http://tinyurl.com/5xxsu5) we can read that PTL has multifaceted antitumor effects toward both MM cells and the bone marrow microenvironment. Excellent starting point, I’d say! Okay, with no further ado, I will plunge right into the study.

 

The beginning of the full study has some interesting wording: Despite intensive chemotherapy, multiple myeloma (MM) remains an incurable, yet chronic, blood cancer with over 14,000 patients diagnosed and 45,000 patients treated yearly in the United States The interaction of MM cells with the bone marrow microenvironment contributes to the heterogeneous treatment response and drug resistance.. Incurable, yet chronic, did you notice that? Hmmm, I think this may be the first study I have looked at so far that mentions the adjective “chronic” in the same breath as “myeloma.” Well, well.

 

Reading on, when myeloma cells adhere to the bone marrow stromal cells (BMSC), that is, to the cells and the supporting tissue that surround the myeloma cells in our bone marrow, NF-kappaB activation in the BMSCs up-regulates interleukin-6 (IL-6) and vascular endothelial growth factors, which further enhance MM cell growth both directly and, in the case of vascular endothelial growth factor, also indirectly via promoting angiogenesis. Vascular endothelial growth factor is abbreviated as VEGF and, in a nutshell, is a tumour-feeder.

 

The researchers identify NF-kappaB as the main culprit in the myeloma proliferation process, since it affects both the tumor cells and the supporting microenvironment.

 

Interesting titbit: one of the anti-myeloma strategies criticized by the Indiana researchers is the use of Bortezomib (Velcade), in this sense: the proteosomal inhibition in normal cells can lead to significant side effects due to the accumulation of toxins, which would otherwise be removed by a fully functional proteosome. The Indiana researchers argue that targeting NF-kappaB might instead lower toxicities while maintaining efficacy. Hmmm.

 

Now, since I know a few myeloma folks who are taking dexamethasone, here is some info on PTL used with dex. The researchers found out that this combination is synergistic.

Here is the gist: Parthenolide activates both the extrinsic and intrinsic apoptotic pathways, whereas other anti-MM treatments, including conventional chemotherapy, radiation, and glucocorticoid, primarily activate the intrinsic apoptotic pathway. We hypothesize that simultaneous activation of both apoptotic pathways may enhance cytotoxicity. Our finding of an additive cytotoxicity with the parthenolide and dexamethasone combination supports this concept.

 

Parthenolide also attenuated the protective effect of the bone marrow microenvironment on myeloma cells. And IL-6 was unable to protect the myeloma cells from the toxic effect of this powerful plant extract. For the scientifically-minded: Parthenolide inhibited the NF-kappaB–DNA binding and further reversed the effect of TNF-alpha–induced NF-nB activation.

Sometimes I read Science Daily articles only because I am intrigued by the titles, as in this case: “Nanotechnology risks: how buckyballs hurt cells” (see: http://tinyurl.com/59za7j)
Buckyballs??? Hmmm. 

At first, I thought the word had to have been coined by a scientist with a quirky sense of humour, but it turns out that buckyball is simply the short version of “buckminsterfullerene,” named (because of its dome-like shape) after the U.S. architect R. Buckminster Fuller (aha!), who designed geodesic domes.

 

But wait, I haven’t said what they are: strong, heat-resistant and revolutionary nanosized particles that are already being made on a commercial scale for use in coatings and materials. The article unfortunately does not specify which coatings and materials…but I found that some of their potential uses would be in MRIs (in the form of bigger buckyballs called trimetaspheres) and drug delivery systems.

 

But, and there is a but!, buckyballs have been shown to cross the blood-brain barrier and alter cell functions. Wait a sec, I don’t know about you, but that sounds rather sinister to me!

And, in fact, tests have demonstrated that buckyballs cause brain damage in fish, and inhaling carbon nanotubes results in lung damage similar to that caused by asbestos. Nanotubes, by the way, are like elongated buckyballs.

 

Altered brain cells. Lung damage. Asbestos. Say no more.

 

You can keep your buckyballs…

Thanks to Sherlock, who found and sent me the link (grazie mille!), I was able to listen to the presentation given by Dr. William H. Matsui (leader of the Johns Hopkins University myeloma stem cell team) at the April 12-16 annual meeting of the American Association for Cancer Research, or AACR. Dr. Matsui’s presentation, titled “Targeting cancer stem cells in multiple myeloma,” is a brilliant review of myeloma stem cells versus normal stem cells, cyclopamine, the Hedgehog signaling pathway, GRN163L, why myeloma patients relapse and so on. A lot of info!

 

Here is the link: http://tinyurl.com/4kf9mu If for some reason it doesn’t work for you, then just go to the AACR homepage, look on the right-hand side and click on Annual Meeting 2008. Then do a search for “Matsui,” and you will be directed to the correct page. It takes a minute or so to load the slides and whatnot, so please be patient.

 

One more thing: the presentation is almost 42 minutes long and a bit on the technical side, so be prepared. But I found it fascinating, and it gave me a lot of food for thought…and for future posts!