Tests and games

Just a quick post today because Italy is playing against France this evening…the European soccer championship, you know…and I am too excited and worried to do any research. I suppose you can guess which flag I will be waving…wink smiley (and no, I don’t care for soccer or indeed sports in general, but when the Italian soccer team is playing I turn into a mad shrieking banshee…).


In answer to the questions concerning my osteoporosis tests, here are the ones that I took in April followed by the ones that my endocrinologist asked me to do next fall:


1. Calcium in the blood and urine; phosphorus in the urine (that was a lab mistake, it should have been a blood test); alkaline phosphatase; bone alkaline phosphatase; parathyroid hormone; creatinine in the blood and urine; creatinine clearance; pyridinoline.


2. In addition to the above, I will have the following tests done in the fall: phosphorus in the blood; vitamin D (25-OH); calcium ion. She also ordered a femoral and lumbar MOC, the abbreviation for Mineralometria Ossea Computerizzata, similar to a bone mineral density test but more comprehensive, from what I read online.


I think that is it. Oh, by the way, my official diagnosis is “hyperparathyroidism of uncertain origin.” (Remind you of anything? wink smiley ) That is why my endocrinologist wants me to suspend my intake of vitamin D until the fall. If I don’t do so, she won’t be able to figure out the cause of my elevated parathyroid hormone.Forza Azzurri!!!  


Okay, enough about tests and whatnot, I need to focus on this evening’s soccer game:
Forza Azzurri!!!


On Sherlock’s wise recommendation, my most recent set of tests (April) included a set of osteoporosis ones. I have two good reasons to be on top of my bone health: 1. my mother, who is almost 80 years old, has osteoporosis, and 2. as we know, myeloma weakens and damages the bones, causing bone pain, fractures and hypercalcemia (too much calcium in the blood due to bone destruction). Bone pain, in fact, is the most common symptom of myeloma at the time of diagnosis.

Well, those results were all within normal limits except for one: my parathyroid hormone levels, paratormone in Italian, were a bit on the high side. Para-whaaat? I had to look this up online. Never heard of it before.


The parathyroid glands are four tiny glands located in the neck. As I learned from an excellent website (http://tinyurl.com/68x78n), they have nothing to do with the thyroid gland except for location: Parathyroid glands are small glands of the endocrine system which are located in the neck behind the thyroid. The thyroid gland controls body metabolism whereas the parathyroid glands control body calcium and phosphorus levels. These four glands produce the parathyroid hormone (PTH) whose only function is to control calcium levels in the blood. If our body calcium is low, the glands produce more PTH to raise calcium levels. If blood calcium levels rise, though, the glands decrease PTH production. This is the normal situation.


But sometimes one or more of the glands can develop a benign tumour that causes it/them to secrete more PTH than needed. Blood calcium consequently rises. This is called primary hyperparathyroidism. The risk of osteoporosis and fractures increases. This is not my case: my blood calcium is the lowest it has ever been.


Secondary hyperparathyroidism or SHPT is instead caused by long-term low levels of blood calcium. It is typical of people with chronic renal failure (again, not my case) or with vitamin D deficiency. Aha! That could well be my case, since SHPT blood tests show elevated parathyroid hormone levels but low or normal calcium levels.


Of course, I also checked Internet to see if there was a connection between hyperparathyroidism and myeloma. There is. This makes sense when you consider that one of the symptoms of myeloma is too much calcium in the blood, as we have seen. But usually, when myeloma patients’ parathyroid levels are high, so are their calcium levels. Not my case. So I was able to exclude myeloma as a cause for my overly active parathyroid glands.


Since I am not a medical doctor, though, at times my interpretation of test results requires confirmation. To make a long story short, I went to see an endocrinologist yesterday morning. I had never been to an endocrinologist. It turned out to be a very interesting visit.


She didn’t seem overly concerned about my highish parathyroid hormone result but told me that it could be caused by one of two things: a. lack of vitamin D (bingo!), or b. a batty gland that can be removed…surgically. Obviously, I hope option “a” turns out to be the correct one. So, what do I need to do? Easy peasy: stop taking vitamin D for 3-4 months and then have my tests repeated. If my parathyroid level increases, that would confirm a diagnosis of vitamin D deficiency. If not, then we will consider the whacky gland option.


The endocrinologist told me that, if she were in my situation, she would do exactly what I am doing–take curcumin etc. (how about that?!!!). She was very matter-of-fact and used very simple words to describe active myeloma as a form of (very very very bad!) osteoporosis that erodes the bone from within. While destroying the bone, it also prevents bone reformation. Nothing new to me, but I was impressed by her knowledge of this cancer.


She also told me that specialists, from haematologists to radiologists, tend to shut themselves inside their highly focused specialistic box and forget to peek outside that little box. She instead strongly believes that it is dangerous to forget that patients may have other things going on that affect their general state of health and that could also be affecting the specific condition under treatment—myeloma or whatnot. She said that we must take care of health issues before they turn into problems instead of waiting until it’s too late. Of course, that is not always possible, but in my case it is because I was diagnosed early.


She told me that we should be “well-equipped” in case my myeloma becomes active some day. I certainly didn’t argue with that!


She also highlighted the importance of physical activity, so I see many walks and treks in my future Smiley face. Stefano and I are now planning our summer holiday that will include at least one natural reserve. Wherever we decide to go, it will be near a park with heaps of nature trails.


In conclusion, I would like to recommend…indeed, highly recommend!…that every myeloma patient go to an endocrinologist and have bone-related tests. Take care of your bones to prevent possible future problems. Of course, those of us who are lucky to be asymptomatic hope to remain so and never develop any of the problems related to this cancer. But…just in case…!!!

The Bathtub Test

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!)

The thunder of God

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 Tripterygium wilfordii Hook.f, or Thunder of God Vine“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. Smiley face I have quite a bit of research in my future, that much is clear!

Busier than busy!

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!

An Italian discovery: IL-12 kills myeloma cells

Vittorio (grazie!; for info in Italian, please see http://mielomahelp.blogspot.com/) told me about an interesting discovery made recently by a team of Italian researchers at the Istituto G. Gaslini in Genoa: interleukin 12 or IL-12 inhibits the proliferation of multiple myeloma in two ways, as we will see below.


But first, what is IL-12? It’s a cytokine or a sort of hormone that is naturally produced by our body, On an Italian scientific website (http://tinyurl.com/3pggpf) I read that it is responsible for regular communication between cells and has various effects on the immune system. Among other things (I read elsewhere), it is closely linked to the activities of T cells and NK (natural killer) cells and also has anti-angiogenic effects.


A few years ago the same group of researchers demonstrated that B cells possess an IL-12 receptor consisting of two parts—part 1 and 2. This laid the basis for their most recent discovery, published in the May 12 2008 issue of “Blood” (see abstract: http://tinyurl.com/58mu5u): part 2 is absent in B-cell lymphomas and leukaemias. Aha! And, get this!, cancer cells proliferate in the absence of part 2.


In order to demonstrate the direct relationship between IL-12 and tumour progression, the Genoa researchers examined cells taken from myeloma patients and tumour cells injected into mice without immune systems. Their tests showed, and I would like to highlight FOR THE FIRST TIME EVER!, that IL-12 strongly (!) inhibits myeloma progression: 1. it blocks the process of angiogenesis (that is, the formation of blood vessels that feed tumours) and 2., yippee!, it also induces the apoptosis (programmed cell death) of myeloma cells.


I don’t know what the next step will be, but it seems that the point would be to reintroduce that missing bit of IL-12 (that is, part 2) somehow…if at all possible. This may not turn out to be a “cure” for myeloma (I found no mention of its ability to target myeloma stem cells…), but, if it can kill some of the blasted circulating cells, well, that would be a good starting point…


Auguri a Stefano!

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! Smiley face). 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!)!

The same in English…

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!”

Parthenolide and myeloma news

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. my feverfew plantShe 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.


And it just so happens that parthenolide inhibits NF-kappaB (as do curcumin and practically every substance that I have researched and posted about here!). Its anti-tumour effects have been observed in various cancers, including breast, lung, prostate, cholangiocarcinoma, and acute myeloid leukemia. It also increases the effectiveness of chemotherapy, which might be of interest to those who are doing chemo right now.

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.

At any rate, the researchers tested parthenolide in myeloma cell lines that had become resistant to dexamethasone and doxorubicin. After 72 hours, PTL inhibited the proliferation of these resistant cells.


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.


Oh, you may ask what “extrinsic” versus “intrinsic” apoptotic pathway means? Good question. Not easy to answer, but basically the death of a cancer cell can be caused by “die, you scoundrel!!!” signals transmitted by so-called “death receptors” located on the cell’s surface, that is, external (to the cell) signals, or by death signals that originate inside the cell such as those deriving from DNA damage or from chemotherapy.

The researchers also found that PTL is toxic only to myeloma cells, not to the surrounding healthy ones. Now, haven’t I read that BEFORE?

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.

The study concludes that parthenolide is effective against MM cells in the context of the bone marrow microenvironment and that its mechanisms of action are both caspase-dependent and independent. In combined therapy, parthenolide is additive and synergistic with dexamethasone and TRAIL, respectively. Our findings provide a rationale for the clinical development of parthenolide. (TRAIL, by the way, stands for TNF-related apoptosis-inducing ligand; basically, it helps induce apoptosis in cancer cells.)

How about that?

Don’t give me any buckyballs!

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…