Stress Involved In Myeloma Progression: Very Evil Growth Factor

Today I will be putting back a couple of posts, including this one, which I posted on December 7, 2007. The original posts were gobbled up by the server, apparently, comments included. I will put the comments back as best I can. Sorry if they look funny! Not funny haha, funny weird. 😉

Other myeloma bloggers have posted about a recent study (abstract: http://tinyurl.com/2w4ndb) showing the link between myeloma and stress. My friend Sherlock sent me the full study, so I will try to provide some additional information. Conducted by a team of researchers at the Ohio State University Medical Center, this study was published in November 2007 in “Brain, Behavior and Immunity,” which by the way looks like a very interesting publication. I must keep my eye on it.

The study is titled “VEGF is differentially regulated in multiple myeloma-derived cell lines by norepinephrine.” A couple of notes before proceeding. Noradrenaline, also known as norepinephrine (NE), is a hormone and neurotransmitter involved in alertness and concentration, among other things. It is involved in heart rate, blood pressure and blood sugar level increases. VEGF stands for “vascular endothelial growth factor,” and is an evil signalling protein that is linked to tumour progression, feeding cancer cells, etc. Read this excerpt from an IMF article written in 2001 (http://tinyurl.com/2yh49k): “Dr. Kenneth Anderson of the Dana-Farber Cancer Center mentioned that VEGF might not only be important for the formation of new blood vessels in MM but also has the potential to stimulate directly the proliferation and migration of myeloma cells. His group demonstrated that production of VEGF by myeloma cells can be stimulated by activation of the CD40 molecule on the surface of the tumor cells.” CD40, we meet again!…remember my CD40 post? I am not done yet with natural ways we can use to inhibit CD40, I just need to find the time to read the studies that Sherlock sent to me.

But let’s get back to VEGF. The Ohio stress study tells us that “VEGF is a crucial cytokine that directs and promotes tumorogenesis and potentiation in the marrow. VEGF levels correlate with overall prognosis and associated bone destruction, which contributes substantially to clinical morbidity.” I told you VEGF was evil! In fact, I suggest that from now on it be known, perhaps more appropriately!, as “Very Evil Growth Factor.”

The introduction begins: “There is evidence that psychological factors can affect the incidence and progression of some cancers.” And, in fact, there is definitely a connection between our IL-6 levels and chronic stress, which is actually a topic on my infinitely long to-be-researched list. That is one reason why I was most interested in the finding, reported in the Ohio study, that NE has been found to stimulate IL-6 and IL-8 in human melanoma cells. But these two cytokines are also actively involved in myeloma. We know all about evil IL-6, but IL-8 has also been connected to progression in myeloma. No comment necessary, methinks.

Discussing a previous study, the Ohio researchers report that stress can inhibit T cells from responding “to tumor-associated antigens on tumor cells of immunogenic tumors.” T cells, hmmm, that sounds familiar.. And the effects caused by stress may “may contribute to tumor progression independent of its effects on the immune system.” Well, we knew that stress is bad for us, but this goes a bit beyond “bad.”The researchers tested three myeloma cell lines in different stages of development. All three had “the potential to respond to NE,” but one in particular “exhibited the greatest NE-dependent response.” Interestingly, this cell line came from someone whose myeloma was aggressive but ”in the earliest (and comparatively longest) clinical phase—i.e., where disease is confined to the bone marrow.” This could mean that in early stages perhaps the blood supply to the malignant cells could be diminished simply by inhibiting NE, which would not kill the malignant cells, of course, but should theoretically slow down tumour growth and disease progression.

Toward the end of the study, we find the following: “Whether the stress-associated activation of the sympathetic nervous system results in the upregulation of NE levels in the bone marrow is unknown. However, observations described here suggest the potential for a stress-associated stimulation of proangiogenic properties of MM cells through the upregulation of NE levels.” The Ohio team adds that “the mechanism involved in the NE-dependent increase in VEGF release by MM cells is not known.”So let’s have more studies like these instead of inanities of the following sort (I glanced at this article this morning and could hardly believe my eyes): “new research suggests that the presence of other people may enhance our movie-watching experiences. Over the course of the film, movie-watchers influence one another and gradually synchronize their emotional responses” (http://tinyurl.com/299s5x). Ehhhh??? You’ve got to be kidding. Isn’t it common knowledge that if you go see a fantastic movie with someone you don’t like, most likely you will hate it, but if you go to see the same movie on your own or with a good friend, you will probably love it, blablabla? Do we really need actual STUDIES to look into this sort of twaddle? Come on!

I would like to finish by saying that I hope to have time at some point to look at the other NE-cancer studies. The one I read today deals specifically with myeloma, but the other NE studies examine other types of cancer. And then there is the whole related issue of beta-blockers, which the Ohio team suggests might be beneficial for myeloma patients (but more info is needed, they add). Anyway, that topic too complicated to get into today. Interesting, though. Okay, have a fun laughing weekend, everyone!

Server Updating

Hi everyone! Just a quick note to reassure those of you who thought (and wrote to me that…) my blog was gone forever! It’s not, it’s not! Though, I must admit that when, first thing this morning, I went to my homepage and noticed that I had “lost” my last few posts, I flipped out for a second or two. But I have been reassured by the fabulous Healthblogs manager that it will all return to normal, photos included. You see, the server is in the process of being updated, so a few glitches are bound to occur. My “old” blog should be reinstated within a few hours or days or centuries or whatever. No worries! Nothing has been lost, including all the wonderful comments that you left me on my most recent test result post. Thank you so very much for those! Anyway, I will keep doing my research and post about it as soon as things return to normal. Now I will try to post this petit message…and see what happens! Poof! 😉

Washing Dishes

A major event occurred yesterday: our dishwasher broke. The technician, funny guy, told us that there was no point in attempting to resuscitate it. He actually called it a corpse. The new dishwasher arrives on Monday. Until then, the corpse will sit in our kitchen mocking us while we (I, most likely) wash dishes by hand. And tomorrow a couple of Stefano’s colleagues are coming over for dinner, is this typical or what? We planned this dinner last week when we had a fully functional machine. The joke’s on us.

How did we ever manage before the dishwasher era? Sometimes I wonder. Yet my family never owned one; we always washed dishes by hand. I never had a dishwasher when I lived alone, either. And it was only after several months of living together that Stefano finally suggested we buy a dishwasher. A DISH-WASH-ER???, I replied, somewhat disdainfully, what would we EVER want with something like THAT?

Eight years later I can barely live without one. I feel lost.

So I have chosen to do nothing much this afternoon. No research, no housework well, except I need to HAND wash the dishes that have piled up since yesterday sigh! 😉

My test results haven’t arrived yet. Next week, probably. I don’t have high hopes for them, to be honest, since I took them during a rather stressful period, when my teaching job had barely begun (stress stress stress!), plus I remember feeling tired all the time. I hope to be proved wrong, of course!

One last note in answer to a couple of questions. I haven’t tried BioCurcumax (which is the same as the Super Bio-Curcumin sold by LEF) yet, so I don’t have an opinion on it. The idea of mixing curcumin with the essential oil of turmeric, though, is a splendid one. That’s all I can say about it right now. Sorry, it’s not much!

Curcumin Restores T Cells

Doing research for a recent post, as frequently happens, I came across an interesting abstract with some hard-to-believe news. My brilliant friend Sherlock (grazie!) kindly sent me the full study, published in the Journal of Biological Chemistry in June 2007. According to the abstract (http://tinyurl.com/3yqzc6), Administration of curcumin to tumor-bearing animals resulted in restoration of progenitor, effecter, and circulating T cells. Curcumin can reinstate our T cells at every stage of their development? No way! (Yes, way). Hmmm, the question arises: why should we care about T cells? Well, if we didn’t have any T cells, we would be like nude mice, yes, the sort used in lab experiments. We would have no way of fighting off disease. T cells, in a nutshell, are crucial players in our immune response to diseased cells.

Let’s take a look at the full study: In order to establish itself, a growing tumor must evade the immune system of the host. This contributes to tumor-induced immune suppression. A growing tumor can evade the proposed immune surveillance by several mechanisms. One of these mechanisms is to kill (induce apoptosis of!) our T cells. Reading on, we learn that Increased oxidative stress because of the growing tumor can be another cause of immune disruptions. Recently, several observations indicate that a chronic inflammatory condition develops in patients with advanced cancer, causing oxidative stress that can shut off immune functions, including those of T and NK cells. Oh, this is not good at all.

Before proceeding, let me just mention that I was confused enough about all these different types of cells that today I looked everything up, from A to Z. I am now in the midst of putting together a brief (!) explanation (?) of a very complex topic. For now, let it suffice that B, T and NK (natural killer) cells are three types of lymphocytes (white blood cells) that originate from hematopoietic stem cells (HSCs), located in the bone marrow. They have different functions, but we don’t need to get into the nitty gritty, yet. If you can’t wait for my explanation, then click on the fabulous link I provide below. Back to the study, now.

A tumour has a negative influence on the production of T cells in the thymus, which is a small organ, located behind the sternum, that produces T cells (the “T” stands for “thymus,” in fact). A tumour causes a massive depletion of both thymic and circulatory T cell populations. Massive depletion of T cells? Yikes. But there is GOOD news. The administration of curcumin brought back thymic CD4+8+, CD4+, and CD8+ cells as well as circulatory effecter CD4+ and CD8+ cells to control level. (CD4 and CD8 are the two main T cell subsets, by the way.) Curcumin brought these cells back to CONTROL level? Well, knock me down with a feather!

Ah, but it gets better. Curcumin protected T cells from being killed by the tumour. When preincubated with curcumin, these cells turned into Superduperfantastic cells, resistant to any tumour attack (sort of like Harry Potter versus Voldemort). In other words, they survived. Oh, sure, this is all happening in vitro. But the researchers experimented with mice, i.e., in vivo, too. Exact same results. They conclude that from aforementioned in vitro and in vivo results, it may be envisaged that curcumin might also protect T cells from a tumor-induced demise in humans. Hey, it’s not every day that I get excited about something called thymic CD4 plus! 😉

My next topic stumped me for hours, it seems, until I came across an absolutely brilliant website that opened up a whole new world for me: the world of relatively easy biology. Itsy bitsy thingies no longer have any secrets for me thanks to John Kimball, a retired biology professor who taught at Tufts and Harvard (I must remember to write him a glowing fan letter). The updated sixth edition of his biology textbook is online (free, too): http://tinyurl.com/57ygj So from now on, if you ever have a doubt about, say, the JAK-STAT pathway, this is the place to go. 😉 Seriously, though, thank you from the bottom of my heart, Prof. Kimball! Everything is crystal clear now. Well…more or less!

Here’s what stumped me: in the curcumin T cell study, I read that tumours downregulate the anti-apoptotic Bcl-2 protein (take my word for it, this is NOT a good thing). But that’s precisely what curcumin does: it downregulates Bcl-2 in myeloma cells. Wait, how could this be? Why is the downregulation of Bcl-2 bad for T cells, good for myeloma cells? Ah, you see, perhaps, had I written out the question, I wouldn’t have spent hours trying to figure it out!

It’s very simple, really. In the case of T cells, in fact, we WANT to have a high level of Bcl-2. In the case of myeloma cells, we don’t. Prof. Kimball’s page on Bcl-2 explains that B cells, like all activated lymphocytes, die a few days after they have had a chance to do their job. This ensures that they do not linger around after the threat has been dealt with and turn their attack against self components. Aging B cells kill themselves by apoptosis. But high levels of the Bcl-2 protein protect the cells from early death by apoptosis. After reading these four sentences, a light went on in my brain: we want T cells to LIVE, but myeloma cells to DIE. Therein lies the difference. Okay, so it took me hours, not minutes, to figure this out, but I am not a biologist, and I didn’t have this wonderful reference text at my fingertips until the latter part of the afternoon.

Well, we have yet another (!) good reason to take curcumin. I can feel my T cells getting more powerful by the second…!

My brain is fried, now, and I need to get off the computer, but will certainly take a second look at this study at some point over the weekend. I would like to end by pointing out that Mary has some good advice for us (see her most recent comment to my December 3rd post). Please go have a look!

Herbs Against Myeloma: Ursolic Acid

The September 2007 issue of Molecular Cancer Research has a fascinating study, co-authored by Prof. Aggarwal, titled: “Ursolic Acid Inhibits STAT3 Activation Pathway Leading to Suppression of Proliferation and Chemosensitization of Human Multiple Myeloma Cells.” The abstract can be viewed here: http://tinyurl.com/2fkrxl As usual, thanks to my friends, I have read the full study. Ursolic acid can be found in rosemary, apples, bilberries, cranberries, pears, peppermint, lavender, oregano, holy basil, thyme and prunes. There are a ton of studies on the anti-cancer effects of this plant extract, but today I want to focus on this one in particular.

First, a word or two on STAT3. According to one of the main studies on myeloma and curcumin, published in 2003 in the Journal of Immunology (full text: http://tinyurl.com/397tow), STAT3, which stands for Signal Transducer and Activator of Transcription 3,” is a cell signalling protein and a prime anticancer target because it can protect cancer cells from apoptosis. Curcumin inhibits the activation of STAT3, quelle surprise. Another inhibitor of STAT3 is capsaicin (see my capsaicin Page on the right): Capsaicin down-regulated the expression of the STAT3-regulated gene products, such as cyclin D1, Bcl-2, Bcl-xL, survivin, and vascular endothelial growth factor. I used to shun spicy hot foods, but since reading the studies on capsaicin, I have begun sprinkling spicy red pepper on my food. And now I really like it. Yesterday I made an organic vegetable and free-range chicken soup (Stefano has a cold, poor dear) with the usual ingredients (garlic, onions and vegetables of all sorts), to which I added a Southern Italian hot red pepper mamma mia!, together with a bit of every single herb we have in the garden and in the house (oh yes, turmeric, too!) and a big piece of ginger. Delicious!

Back to us. The ursolic acid study tells us that STAT family proteins have been shown to play an important role in tumor cell survival and proliferation, and in particular STAT3 is often constitutively active in many human cancer cells including multiple myeloma, leukemia, lymphoma, and solid tumors. It can be activated by IL-6 (interleukin-6), by the way. Without going into too much detail, what we want to do, clearly, is inhibit STAT3. One way is through DIET, that is, eating foods that contain ursolic acid. So much for my being told, back in 2005, that there was nothing I could do to stop the obvious (by then) progression from MGUS to MM. Drat. I wish I had known back then a fraction of what I know now. But, as the saying goes, better late than never/meglio tardi che mai! 🙂

The study tells us that Ursolic acid is a pentacyclic triterpenoid that has been shown to suppress the growth of various hematopoietic tumors, inhibit tumor promotion, and inhibit tumor angiogenesis. We have recently shown that ursolic acid is a potent inhibitor of nuclear factor-kB (NF-kB) activation pathway, which is activated by inflammatory agents, carcinogens, and tumor promoters. In this study, the researchers wanted to test their theory that ursolic acid suppresses the STAT3 pathway in myeloma cells. They were successful.

The following will be of interest in particular to those taking Velcade and Thalidomide: In our experiments, ursolic acid indeed suppressed both constitutive and inducible STAT3 activation. This inhibition decreased cell survival and down-regulated expression of proliferative and angiogenic gene products, leading to suppression of proliferation, induction of apoptosis, and enhancement ofthe response to the cytotoxic effects of thalidomide (an inhibitor of tumor necrosis factor expression) and bortezomib (a proteasome inhibitor; also called PS341) in multiple myeloma cells. Further on, we read that ursolic acid significantly enhanced the apoptotic effects of thalidomide from 20% to 70% and of bortezomib from 25% to 80%. Now, those are significant numbers, I’d say!

I cannot examine every single bit of information provided by the study, but for instance ursolic acid increased the expression of Bax and Bak proteins, which cause apoptosis in myeloma cells. Yeah! Also, similarly to capsaicin, ursolic acid suppresses the expression of several STAT3-regulated genes, including proliferative (cyclin D1) and antiapoptotic gene products (survivin, Bcl-2, Bcl-xL, and Mcl-1) and angiogenic gene product (VEGF). Super. At the end of the study we find a reference also to other cancers, including head and neck cancers, hepatocellular carcinoma, lymphomas, and leukemia. They, too, also have constitutively active STAT3. The suppression of constitutively active STAT3 in multiple myeloma cells raises the possibility that this novel STAT3 inhibitor might also inhibit constitutively activated STAT3 in other types of cancer cells.

This is excellent news. Stefano and I grow quite a variety of herbs in our garden, including at least four or five different types of thyme and two of rosemary. We even have an oregano plant. Herbs add taste to any dish, as we know…but using herbs in our cooking goes way beyond taste enhancement, now that we have discovered that ursolic acid inhibits a crucial myeloma survival pathway, inhibits the proliferation of myeloma cells AND induces apoptosis in the same…why, I believe it’s time for a little dance of joy…! And before it gets dark, I really must go outside to gather some rosemary for dinner tonight. 🙂 Ciao!

Lunching With Baicalein

Hah, and you thought that perhaps I was DONE with baicalein, eh? Nope. Not by a long shot. I still have a few baicalein studies to read…Besides, at lunchtime TODAY I will start taking Scutellaria baicalensis, which contains a high percentage of baicalein and also a bit of wogonin. I will also start taking Zyflamend, which is a blend of various herbal extracts (see my page on Polyherbal Zyflamend). Of course, I will keep taking my curcumin-quercetin-cocoa mass-honey mixture at night, since I didn’t give it enough time to work before having blood tests done a couple of weeks ago (I should have my results by next week, by the way). We shall see what happens. Of course, my next set of tests may be influenced by the flu vaccine (which apparently can increase IgG levels for up to six months after administration!), so they may need a bit of interpretation.

Thanks to a friend (thanks you! 😉 ), I got my hands on a very interesting study that I looked at more carefully this morning, even though I really SHOULD BE preparing my English classes for tomorrow, sigh. Published in the November 2007 issue of Clinical and Molecular Allergy, the study is titled: Baicalein inhibits IL-1b- and TNF-a-induced inflammatory cytokine production from human mast cells via regulation of the NF-kB pathway. Let’s quickly examine the title. IL-1beta is an inflammatory cytokine that is a potent inducer of the important myeloma growth factor, IL-6. (see these two Mayo Clinic study abstracts from 2006 and 2007, respectively: http://tinyurl.com/2hu4am and http://tinyurl.com/27ffa4). Anything that induces IL-6 is no friend of mine! I am almost certain that I have already written about TNF-alpha, or tumour necrosis factor-alpha, but just in case I haven’t, here goes: it is a growth and SURVIVAL factor for myeloma cells, albeit not as powerful as IL-6. So, also not good news for us.

A few remarks on human mast cells. As the abstract (see: http://tinyurl.com/24f2ge) informs us, these are multifunctional cells capable of a wide variety of inflammatory responses. According to the full study, these cells accumulate wherever there is an inflammatory process going on and even mediate the production of inflammatory cytokines. Now, that’s really no good, no good at all, especially since Inflammatory cytokines are important factors in chronic inflammation, allergy, asthma, atherogenesis, and autoimmune diseases. Reading on, we are told that mast cells have been implicated in acute and chronic inflammatory responses and in many diseases characterized by inflammation. Oh, and read this: activated mast cells secrete IL-6! Tsk, tsk. Bad BAD mast cells!

Another interesting bit: The activation of NF-kB requires phosphorylation and proteolytic degradation of the inhibitory protein IkBa. This sentence takes us back to the discussion section of the 2005 Blood study on baicalein and myeloma (full text: http://tinyurl.com/2jnlej). I quote: NF-kB regulates the expression of many genes (IkB-a, Bcl-xL, IL-6, and cyclin D1) important for the proliferation and survival of myeloma cells.

Well, on page 16, the November 2007 study states: The results suggest BAI inhibits the NF-kB activation via inhibition of IkBa phosphorylation and degradation. BAI, by the way, stands for baicalein.

Hmmm, how about THAT? So, is it lunchtime yet? 😉

Scutellaria Baicalensis/Baicalein Update

I am doing the groundwork for my Scutellaria baicalensis experiment, which has brought me to view a few new studies, such as one published in the November 2007 issue of “Molecular Cancer Therapeutics,” see abstract: http://tinyurl.com/266g6y (many thanks to a new friend for sending me the full study AND also to my friend Sherlock for trying to locate it).

Here’s a quick review taken from this study (you can also see my Page on Scutellaria baicalensis). Baicalein, extracted from the root of Scutellaria baicalensis, is an active flavonoid that has been found to have anticancer properties, leading “to cell cycle arrest and suppression of proliferation in cancer cells. And yes, in case you were wondering, that includes myeloma cells in vitro only, thus far. Hence, my upcoming experiment…on myself.

Baicalein (just like curcumin, let me add: see my link to the article on curcumin and survivin, right-hand side of my homepage) reduces the expression of survivin, a protein that inhibits apoptosis in cancer cells, including myeloma cells. If you need convincing that survivin (not to be confused with the adjective “SURVIVING,” by the way!) has relevance for myeloma, take a look at this February 2007 Leukemia abstract: http://tinyurl.com/2s9xon My comment: survivin may be fascinating, but, according to the above-mentioned Molecular Cancer Therapeutics study, it is associated with decreased survival, unfavorable prognosis, and accelerated rates of recurrences in cancer therapy. Nothing “fascinating” about that, methinks…

Anyway, the Molecular Cancer Therapeutics study suggests that the inhibition of CDC2/cyclin B1 by baicalein contributes to the reduction of survivin and the proliferation inhibition in cancer cells. CDC2 is a kinase also present in myeloma…hmmm. Six flavonoids, baicalin, catechin, genistein, quercetin and rutin, in addition to baicalein, were examined by these researchers. The most toxic to bladder cancer cells was found to be baicalein, which was, and, this is significant!, NOT toxic to healthy cells. Does that sound familiar?

I have read the same thing over and over again: Toxic to cancer cells, Not Toxic to healthy cells! Okay, so where ARE the clinical trials!?! Well, quelle coincidence (!), since I wrote my May 31st post on Scutellaria baicalensis, two more clinical trials testing Scutellaria-derived substances have been added to the one I mentioned. One is testing an aqueous extract from herba Scutellaria Barbata D. Don on metastatic breast cancer patients; the other is testing a botanic formulation called PHY906, consisting of: Scutellariae baicalensis Georgi, white peony root, licorice, and the fruit of Fructus ziziphi (date). According to the patent application (see: http://tinyurl.com/28sfez), This specific formulation was established more than 1500 years ago for the treatment of diarrhea, abdominal spasms, fever, headache, vomiting, nausea, extreme thirst, and subcardial distention,” and “each herb possesses a distinct pharmacological profile that includes anticancer and antiviral activity, hematological and immunological stimulation, analgesic activity, vasodilation, liver protection, antioxidation, and appetite improvement. PHY906 is being tested together with a chemo drug on advanced pancreatic cancer patients. Well, three trials are better than just one, I suppose. If you want to read more about these trials, just go to http://tinyurl.com/28gasl

Speaking of clinical trials, according to the Molecular Cancer Therapeutics study, Although this study provides the potential cancer therapy of baicalein by human cancerous cells in vitro, the human cancer therapeutics by baicalein or combination of the survivin gene knockdown need to be determined by in vivo model before clinical trials. Moreover, the possible pharmacokinetic and toxicologic barriers need further characterization. Very true, but let me point out that Scutellaria baicalensis has been used as an anti-inflammatory remedy in traditional Chinese medicine for more than 2000 years to treat fevers, hypertension, coughing, and other ailments, according to Drugs dot com (see: http://tinyurl.com/2d5fvj). This brings me to my warnings section.

Warnings: according to the Memorial Sloan-Kettering website, Scutellaria baicalensis MAY cause stupor, confusion, and seizures. Am I worried about that? Naaaah, not in the slightest. In the past, I have taken HUGE doses of antibiotics, even recently (now that I think about it), and if you paid any attention to the list of possible side effects associated with half the stuff you take for common ailments, you wouldn’t let it come within a few meters of you, let alone swallow it (or, worse, have your mother-in-law inject it into your hip, as happened to me earlier this fall when I was forced to take elephant-doses of antibiotics for a case of acute bronchitis…). The only other big warning about Scutellaria is that it may interact with cyclosporine, a drug that suppresses the immune system. And then there are the usual pregnancy or breastfeeding warnings, which don’t apply to my case anyway.

Final note: I would like to take this opportunity to thank the two people who have been sending me the full studies that give more “flesh” to my blog posts. One is my beloved Italian friend Sherlock, the other lives and works in the U.S. Thanks to them, I now have the FULL studies of the abstracts that I quoted in my first baicalein post. And much much more! Thank you so very very very much, both of you. Now, I just have to find the time to read all this stuff…eh!!!

True Or Not, It’s A Great Story!

One of my blog readers (thank you!) sent me this story, which gave me quite a few chuckles. Before telling the story, though, I just wanted to reassure all of Peekaboo’s many fans that she is doing just fine, scampering about, terrorizing the other cats…in sum, she’s as mischievous as ever! Ok, here goes:

The following concerns a question in a physics degree exam at the University of Copenhagen: “Describe how to determine the height of a skyscraper with a barometer.”

One student replied: “You tie a long piece of string to the neck of the barometer, then lower the barometer from the roof of the skyscraper to the ground. The length of the string plus the length of the barometer will equal the height of the building.”

This highly original answer so incensed the examiner that the student was failed immediately. He appealed on the grounds that his answer was indisputably correct, and the university appointed an independent arbiter to decide the case. The arbiter judged that the answer was indeed correct, but did not display any noticeable knowledge of physics. To resolve the problem, it was decided to call the student in and allow him six minutes in which to provide a verbal answer which showed at least a minimal familiarity with the basic principles of physics. For five minutes the student sat in silence, forehead creased in thought. The arbiter reminded him that time was running out, to which the student replied that he had several extremely relevant answers, but couldn’t make up his mind which to use. On being advised to hurry up the student replied as follows:

“Firstly, you could take the barometer up to the roof of the skyscraper, drop it over the edge, and measure the time it takes to reach the ground. The height of the building can then be worked out from the formula H =0.5g x t squared. But bad luck on the barometer.”

“Or if the sun is shining you could measure the height of the barometer, then set it on end and measure the length of its shadow. Then you measure the length of the skyscraper’s shadow, and thereafter it is a simple matter of proportional arithmetic to work out the height of the skyscraper.”

“But if you wanted to be highly scientific about it, you could tie a short piece of string to the barometer and swing it like a pendulum, first at ground level and then on the roof of the skyscraper. The height is worked out by the difference in the gravitational restoring force T = 2 pi square root (l / g).”

“Or if the skyscraper has an outside emergency staircase, it would be easier to walk up it and mark off the height of the skyscraper in barometer lengths, then add them up.”

“If you merely wanted to be boring and orthodox about it, of course, you could use the barometer to measure the air pressure on the roof of the skyscraper and on the ground, and convert the difference in millibars into feet to give the height of the building.”

But since we are constantly being exhorted to exercise independence of mind and apply scientific methods, undoubtedly the best way would be to knock on the janitor’s door and say to him ‘If you would like a nice new barometer, I will give you this one if you tell me the height of this skyscraper’.”

The student was Nils Bohr, the only Dane to win the Nobel prize for Physics. 🙂

O animal grazioso e benigno, che visitando vai per l’aere perso

Siede la terra dove nata fui
su la marina dove ‘l Po discende
per aver pace co’ seguaci sui.
Amor, ch’al cor gentil ratto s’apprende
prese costui de la bella persona
che mi fu tolta; e ‘l modo ancor m’offende.
Amor, ch’a nullo amato amar perdona,
mi prese del costui piacer sì forte,
che, come vedi, ancor non m’abbandona.
Amor condusse noi ad una morte:
Caina attende chi a vita ci spense.

Totally off-topic today. Sometimes we need that. Or I do, at least! 😉

A while ago I read online that Roberto Benigni, an Italian actor and film director, is the equivalent of a double shot of espresso coffee. I agree. Some of you may remember him excitedly jumping onto the backs of seats during the 1999 Academy Award ceremony after his La vita è bella, or Life is beautiful won three Oscars. Deservedly so, in my opinion.

Anyway, I am writing about Benigni because yesterday evening he put on an extraordinary one-man show on TV (Rai Uno, one of the Italian state channels). Absolutely brilliant. After a bit of contemporary political satire, Benigni, using his unique expressive communication style, launched into a passionate and eloquent explanation of the Divine Comedy’s 5th Canto. For two and a half hours, he barely stopped to take a breath. Fantastico. I was glued to the screen. Verse by verse, at times word by word, Benigni described every detail of this famous Canto, which centers on the tragic story of two lovers, Paolo Malatesta and Francesca da Rimini. He put into plain language the most intricate and difficult passages and concepts, at times drawing on current Italian social and political events to make his point more clearly. Keep in mind that Dante Alighieri wrote the Divine Comedy in vernacular Italian at the beginning of the 14th century, so this wasn’t as easy as it sounds.

I would like to note that I went through the Italian public school system (yep, I am one of those odd bilingual creatures), where I studied Dante’s Divine Comedy. I also examined each and every verse while doing research for my Ph.D. thesis (don’t ask! 😉 ). My interest, however, has always been superficial…related to schoolwork. But yesterday evening Benigni infected me with his fervour. I want to reread the Divine Comedy.

Benigni ended his performance by reciting the entire 5th Canto from memory. Now, I am no lover of poetry, but this final part brought tears to my eyes. Benigni’s declamation came from the gut, it had feeling, it had passion. Last year, for his interpretation of Dante, Benigni was nominated for the Nobel prize in literature. He didn’t win, but in my opinion, he should have. Grazie, Roberto!

Peekaboo Update, New (Cancer) Stem Cell Clinical Trial And Another Good Reason To Take Curcumin

Peekaboo came home yesterday and is doing well. I went to pick her up at the vet’s at 5 PM. I had to keep her separated from the other cats until this morning so I put her in my parents’ room. She was not very steady on her feet and kept bumping into things (the litter box, the furniture ). I stayed with her until Stefano got home, then we took turns eating dinner so that one of us could be with her (we tried to leave her alone, but she howled). I know, only big-time cat lovers will understand this! 🙂 I spent the night in my parents’ room with Peekaboo, and Stefano slept with the other cats in our room. We have so rarely slept apart in all the years we have been together so, yes, last night was very odd. Anyway, Peekaboo was very happy to be home, nestled in my lap all evening, purring like mad and batting her blue eyes at me. She even did something she has never done before: she kneaded my legs. Cutie pie. This morning she isn’t jumping around like she normally does, but she seems just fine. A bit subdued, that’s all. To be expected.

I have a ton of things to post about, lots of news, but new things keep popping up in my e-mail box just as I think I have finished doing all my research and writing. Aaargh! So I have more reading to do today. In the meantime, I will post about a new clinical trial: http://tinyurl.com/2ap4k8 Yesterday the Geron Corporation announced that it has enrolled the first myeloma patient in its GRN163L clinical trial. GRN163L is a novel inhibitor of telomerase, an enzyme that is expressed in all major types of cancer cells. This enzyme is essential for malignant cell growth and is absent or expressed transiently at low levels in most normal adult tissues. The most interesting aspect of this trial, however, as a MMA list member pointed out yesterday, is that GRN163L has been shown to target cancer STEM cells. Just like DMAPT (from parthenolide or feverfew). Now, if we can get rid of cancer stem cells, the ones that are resistant to conventional treatments and that cause cancer (myeloma, too, of course) to recur well, let’s just digest the implications of THAT statement…! 🙂

Today another MMA list member posted about a study in this month’s issue of “Blood” discussing how the Notch signaling pathway, a new one to me!, protects myeloma cells from apoptosis (death). You can read the abstract here: http://tinyurl.com/ysv9gg Well, I immediately, as usual!, googled Notch signaling and curcumin, and to my surprise (I wonder WHY I am still surprised…!), I found that, yes, apparently curcumin inhibits this signaling pathway (important, by the way, for cell to cell communication), see this 2006 abstract on pancreatic cancer cells in vitro: http://tinyurl.com/2cjgpr See also this December 2007 abstract on leukaemic cells: http://tinyurl.com/2hp5z2 I don’t have time to do more research on Notch and curcumin today (busy in other fields…), but it’s always good to come across another good reason to be taking the orange powder! Yeah!