Holy cats! I just read a rather unsettling Science Daily article (see: http://tinyurl.com/au9kzb). A new study shows that angiogenesis-inhibiting drugs may turn a blissful “well-fed” cancer into an angry aggressive type.

 

A group of U.S. and Spanish researchers found that mice first infected with pancreatic cancer and glioblastoma and then treated with the anti-angiogenic drug sunitinib responded rather well in the beginning…but, after a few weeks, there was an adaptive response by the tumor. The glioblastomas increased invasion into adjacent normal tissue. The pancreatic tumors also became more invasive and, in addition, metastasized to the liver.

 

This study suggests that tumours have a remarkable ability to develop survival strategies. If their blood supply is cut off, they will find other ways to feed themselves and survive…apparently, by spreading and becoming more dangerous. A scary thought indeed.

This article led me to reflect, once again, on the use of aggressive treatments versus gentler, less invasive ones…

A blog reader (thanks!) sent me the link to a food-for-thought 2003 Swedish study (see http://tinyurl.com/d4qc38) on nicotinamide, a water-soluble member of the vitamin B family (specifically, the amide derivative of vitamin B3).

 

Now, this study doesn’t examine myeloma but is still relevant to us because it shows that nicotinamide inhibits IL-1 beta (=SMM-MM progression factor), IL-6 and TNF-alpha by, tadaaa!, 95%. I repeat, by 95%. And it also inhibits IL-8, an angiogenesis cytokine in myeloma, by 85%. This is all most intriguing.

 

This was an in vitro experiment, conducted on healthy human blood incubated with endotoxin, which stimulated the response of the above-mentioned cytokines. Nicotinamide, when added to the mix, inhibited all four cytokines, which is great news. The researchers conclude: As the proinflammatory cytokine response of IL-1beta, IL-6, IL-8 and TNFalpha following endotoxin stimulation of human whole blood is profoundly inhibited by nicotinamide, nicotinamide may have a therapeutic potential as a modulator of cytokine effects in inflammatory disease. Super duper!

 

Now, the study kept mentioning this thing called PARP…no idea what that was, so I had to look it up. The acronym stands for “polyadenosine-5′-diphosphate-ribose polymerase.” Uhm. Okay, spelling it out doesn’t help matters. Forget the acronym.

 

Let’s see (flip flip flip…flipping virtual pages)…ah, here we go: PARP is basically a protein linked to DNA repair, cell proliferation and apoptosis. Interesting factoid: NF-kappaB cannot be activated unless PARP is also activated, as we can see by glancing at this 1999 abstract: http://tinyurl.com/b8hmsc.

 

And, of course, PARP is involved, not in a good way, in myeloma. Hah!

 

A 2005 abstract (http://tinyurl.com/dkyk39) tells us, in fact, that the outcome of PARP cleavage is the apoptosis (=programmed cell death) of myeloma cells. PARP whaaat??? Oh, okay, simply put, PARP cleavage has nothing to do with embarrassingly low necklines but is a typical manifestation of apoptosis. Basically, anything that induces PARP cleavage in myeloma (or any type of cancer) cells is a good…anything.

 

So…my next step was to check out PARP cleavage and curcumin. Well, quelle surprise!, curcumin induces PARP cleavage in myeloma cells (see, e.g., the 2003 MD Anderson curcumin-myeloma study to which I link from my blog): Suppression of NF-kB by curcumin also led to apoptosis of MM cells, as indicated by activation of caspases and cleavage of PARP. So this cleavage business is one of the ways that curcumin annihilates myeloma cells. Good to know.

 

I took this all a bit further. Not surprisingly, parthenolide also induces PARP cleavage in myeloma cells (see: http://tinyurl.com/bdbqzj): Parthenolide rapidly induced caspase activation and cleavage of PARP […]. Capital, capital.

 

Other substances that induce this important cleavage process (perhaps not specifically in myeloma, though; I would need more time to check that out) are:

DHA (omega-3), see: http://tinyurl.com/d4eje2

Quercetin: http://tinyurl.com/cusjx9

Resveratrol: http://tinyurl.com/alfd25

Capsaicin: http://tinyurl.com/dn325k

 

Okay, enough, enough, I don’t have the time to go down the list of supplements on my blog. But anyway, wanna bet that most if not all induce PARP cleavage in some type of cancer?

 

As soon as I finished reading the nicotinamide study, I went downstairs and took my vitamin B supplement (a gooey but tasty liquid with other things in it, too). I take it only now and again, when I need an energy boost…but perhaps now I will begin taking it more frequently. Hey, you never know…

 

Quick consideration. Funny how we tend to overlook things that we don’t understand or don’t think are important. Selective memory, eh? You see, I don’t remember any mention of PARP cleavage in the MD Anderson 2003 curcumin study, a study that changed my life. Yet PARP is mentioned in that study as many as 15 times (I just counted ’em)! But all that mattered to me back then was that curcumin killed myeloma cells. How this actually occurred was not important. Now, though, after three years of research, I am a bit more interested in understanding the mechanics of these apoptotic processes. Not easy…for an unscientific mind…like mine. Oh, how I wish I had a photographic memory!

 

Fascinating bit of news. According to a Science Daily article (http://tinyurl.com/bbvgc3), a study, published in February in the journal “Sleep,” shows a link between sleep duration and the production of cytokines…mainly, IL-6 and C-reactive protein or CRP. Okay, that really caught my attention, since both are involved up to their ears in myeloma progression.

 

Let’s take a quick look. Each additional hour of self-reported sleep duration was associated with an eight-percent increase in C-reactive protein (CRP) levels and a seven-percent increase in interleukin-6 (IL-6), which are two inflammatory mediators. In contrast, each hour of reduction in sleep measured objectively by polysomnography was associated with an eight-percent increase in tumor necrosis factor alpha, another pro-inflammatory cytokine.

 

So if we don’t go to sleep at all, our CRP and IL-6 levels will go way down (good), but at the same time our TNF alpha levels will go up (bad, but I am more concerned about IL-6 and CRP in myeloma). Hmmm. Okay, I am now seriously thinking about sleeping less…no, no, wait, there is some bad news…the less we sleep, the more we increase our chances of developing diabetes, hypertension and obstructive sleep apnea. Oh, phooey! Uffa! And there is more…

 

Another Science Daily article (see http://tinyurl.com/cclaml), published last fall, tells us that loss of sleep can prompt one’s immune system to turn against healthy tissue and organs. Er, not sure I like the sound of that…In fact, we have a better chance of avoiding heart and autoimmune diseases if we get a good night’s sleep. And, incidentally, the researchers in this particular study measured our old friend, NF-kappaB., which turned out to be higher in women who were sleep-deprived. Hah. And more…

 

A related issue. According to HealthDay (http://tinyurl.com/9cvhl6), our immune systems work better at night: Stanford University research with fruit flies reveals that the immune system fights invading bacteria the hardest at night and the least during the day. Stanford University researchers found that fruit flies, whose genetic makeup is incredibly similar to ours, were better able to fight bacterial infections at night than during the day. Well, this would seem to support one of my gut feelings: that it is better to take curcumin and other supplements late in the day, when the body’s metabolism slows down.

 

Just for the heck of it, I looked up sleep and immune function on PubMed, where I found loads of studies. This 2009 one (full study: http://tinyurl.com/ard2yd), for instance, tells us that Species that have evolved longer sleep durations appear to be able to increase investment in their immune systems and be better protected from parasites. Indeed, further on the researchers suggest that sleep fuels the immune system and say that antibody responses and natural killer cell activity are reduced following sleep deprivation. And, in the Discussion part: Our results suggest mammalian species that spend more time asleep are able to increase investment in their immune systems, and thus are better protected from parasitic infection. Well, that explains why I slept almost all the time when I had pleurisy a couple of years ago, and why we sleep more when we have any sort of infection…interesting!

 

In conclusion. More sleep = higher CRP and IL-6 (bad) BUT also higher immunity and less susceptibility to heart/autoimmune diseases (good). Less sleep = lower TNF alpha (good) BUT higher NF-kappaB (only in women, though), lower immunity and increased susceptibility to diabetes, hypertension, sleep apnea, parasitic infections and heart trouble (bad bad bad).

 

Let’s see…hey, isn’t it about time for my nap/pisolino now??? (hehe)

Yesterday Stefano and I went to Siena, to an art exhibit examining the link between madness and art, mental disorders and creativity. The title states it clearly: “Art, Genius, Folly.” We saw works by Van Gogh, Edvard Munch, Antonio Ligabue and many others…a total of 400 paintings and sculptures from the past three centuries. One that struck my fancy was a curious painting attributed to Hieronymus Bosch, the “Concert in the Egg.” (see here: http://tinyurl.com/ap95qn). Overall, an interesting exhibit, at times a bit distressing, especially the initial part, devoted to how mentally disturbed patients have been treated throughout the centuries, beginning in the Middle Ages.

 

The art exhibit’s official website (in Italian): http://www.artegeniofollia.it/

News in English: http://tinyurl.com/c3kjrh

 

Afterwards, we walked around Siena and spent time photographing my favourite piazza in the world, Piazza del Campo. It was a beautiful day, and, by noon, also quite warm, about 15° Centigrade. The piazza was half-filled with people sunning themselves, sitting or lying down on the red-brick shell-shaped slope, reading a newspaper or a book. Little kids chasing after pidgeons. Families picnicking. It was so relaxing.

 

On our way back to Florence, we stopped in Monteriggioni, a fortified Medieval hilltop village in the province of Siena, built in the 13^th century. Monteriggioni (my new blog banner, by the way, is from a photo I took from a distance of this town’s circular walls) is extremely well-preserved and has not undergone any significant changes throughout the centuries. Thanks to Monteriggioni’s fortified walls and strategic position, its inhabitants were able to resist many attacks by the Florentines during the Middle Ages. My first photo of Monteriggioni (above) is taken just outside one of the town gates. The others (below) are inside views. 

 

From Wikipedia I learned that the Italian poet Dante Alighieri used the towers of Monteriggioni “to evoke the sight of the ring of giants encircling the Infernal abyss”:

 

‘però che, come su la cerchia tonda

Montereggion di torri si corona,

così la proda che ‘l pozzo circonda

torreggiavan di mezza la persona

li orribili giganti, cui minaccia

Giove del cielo ancora quando tuona.’

-Dante Alighieri, Inferno, Canto XXXI, lines 40-45

 

‘As with circling round

Of turrets, Montereggion crowns his walls;

E’en thus the shore, encompassing the abyss,

Was turreted with giants, half their length

Uprearing, horrible, whom Jove from heaven

Yet threatens, when his muttering thunder rolls.’

-as translated by Henry Francis Cary during the years 1805–1844

 

Final note: this is a sad period for some myeloma list members/bloggers. Teresa’s husband (see The Beast) just passed away. My heart goes out to her and her family. Another distressing item: a friend’s husband, a myeloma patient, is in the hospital, fighting for his life, after catching some sort of resistant bug and coming down with double pneumonia. Well, I hope to have some good news soon.

 

And this brings me to the following. Some blog readers have asked me about my “feverfew” blood tests. Well, I haven’t had any tests since November 2008. And, since the flu season is still going strong here, I have decided that I cannot and will not risk going up to the hospital lab for blood tests right now. I have postponed having tests done until the end of this month, at least. My feverfew experiment has lasted longer than predicted, unfortunately. But…better be safe than sorry!

A dear friend (grazie!) sent me a study on pomegranates yesterday morning. In the bibliography, I found a 2005 study (abstract: http://tinyurl.com/dh685b; the full study is free, too) discussing a substance called PFE, or pomegranate fruit extract. The exciting bit is that PFE inhibits IL-1 beta, which, as you may recall, is a key player in the progression from smouldering or inactive myeloma to active myeloma. Hah! (My February 1^st and 5^th 2009 posts deal with IL-1 beta and its inhibitors.)

 

Since the full PFE study is available online, I won’t bother going into too many details. Just a few notes.

 

Let’s start with a sentence in the abstract: Interleukin (IL)-1beta induces the expression of matrix metalloproteinases (MMPs) implicated in cartilage resorption and joint degradation in osteoarthritis (OA). Okay, so this study doesn’t specifically mention multiple myeloma, but it is still relevant to us. You see, MMPs are enzymes that play a role in bone destruction and neoplastic growth (they contribute to angiogenesis, e.g.). I read that our myeloma cells actually produce MMPs in order to hollow out our bones…at any rate, simply put, MMPs are evil, evil thingies, and anything that inhibits them is good. As is anything that inhibits IL-1 beta.

 

Well, this pomegranate extract fits the bill. It inhibits the expression of IL-1 beta-induced MMPs. Since I love pomegranate seeds and juice in my salads, that is FABULOUS news indeed! Now I am sorry that I didn’t freeze any pomegranate seeds at the end of last summer…ah, bummer!

As I have written in other posts, back in 2005, after reading the words “mieloma multiplo” on my bone marrow biopsy test result, I burst into tears. Even though I had known for quite some time that my benign condition might progress to malignant myeloma, those two little words punched me right in the stomach. (Note: this was the pre-curcumin era.)

 

Stefano, my husband of almost 10 years now and partner of 13 years, put his arms around me and just held me. I could feel him trembling, so I knew that he was upset, too. But, other than that, he showed no outward emotion…

 

Well, ever since then, I have been worried about him. And, occasionally, believing that it was for his own good, I have quizzed him…how does he feel about possibly losing me to myeloma at some point in the future? Why does he almost always put up an invisible shield and dodge my questions? Why, why, why? “It’s not healthy for you to keep your emotions bottled up inside,” I would say to him. And that is what I thought…until yesterday.

 

That is when I read a Science Daily article (http://tinyurl.com/ckupne) on how different people cope, differently!, with tragic events. My myeloma cannot be compared to a plane crash, of course, but after reading the above-mentioned article, I feel much reassured about Stefano’s coping strategies.

 

It seems, in fact, that there is no “right” way to cope. If people want to express their feelings openly, like I do, fine. But if they don’t, then it’s not good to force them or make them feel that there is something wrong with not talking “about it.”

 

As a result, I won’t bug Stefano anymore. Er, well, okay…at least, I will try!

Since I am a bit tired right now and don’t feel like doing any research or editing (zzz!), I am going to write about one of my students, a slender man, about my age, with an irresistible twinkle in his eye. Let’s call him Phil. I have been teaching Phil English for about a year and a half, now. Until this morning, though, I had NO idea how dangerous this meek-looking man could be. It turns out that he is an evil prankster. Here are just a few of the practical jokes he has played in the past on unsuspecting victims…

 

Phil’s “criminal” career began early, when he was but a child. For instance, Phil would fill his grandfather’s slippers with icky goo while the dear man took his afternoon nap. You can imagine what happened when, still half asleep, his grandfather slipped his feet into…yuuuck!

 

The adult Phil worked for several years in a leather company in Florence. One of his colleagues was a Ms. Perfect, a prim and proper lady who always wore THE perfect outfit, THE perfect makeup, THE perfect accessories. Never a hair out of place. Well, once, on a rainy day, Phil sprinkled an entire bottle of talcum powder inside her umbrella. After work, she grabbed the umbrella, went outside and opened it…right over her head, as it happened. POOF! A cloud of talcum powder covered her…from head to toe.

 

Another day Phil announced that he was about to get married. A few days later, he showed up at work carrying a wedding cake with a bride and groom on top and also some bomboniere. These are typical Italian wedding “favours,” which consist of five sugared almonds symbolizing health, wealth, happiness, fertility and long life. The almonds are usually placed inside small tulle or organza sachets together with some stupid little trinket.

 

The bomboniera tradition is still alive in Italy, although the useless, and expensive!, trinkets are being replaced, thank goodness!, by contributions to charitable organizations. But almonds are still offered to wedding guests. Before Stefano and I got married, we spent HOURS putting together our bomboniere, counting the almonds, putting them inside the sachets, adding tiny fake flowers and trying to tie the tiny little ribbons…Can you tell that I believe that certain traditions should be abolished??? Except that some of the sachets that I have collected over the years (why on earth have I kept them???) and was attempting to photograph just now provided a certain amount of entertainment for Peekaboo, as you can see…by the way, our wedding “trinket,” a ceramic spoon rest made by a potter friend in the United States, can be seen in the foreground. We wanted it to be useful, at least.

 

At any rate, Phil did such a good job of tricking his colleagues into believing that he had gotten married that he was showered with wedding gifts for days. Hmmm, I forgot to ask if he returned them…

 

Another story. One of Phil’s colleagues kept a milk carton in the fridge for his morning caffelatte. One day, Phil carefully opened a brand new carton, finished off the milk and filled the empty carton with water. He then sealed it back up again. And waited…

 

The following story finally convinced me that Phil (I am quite fond of him, you see) has an evil streak. One day, Phil opened another colleague’s container of plain white yogurt. He ate or got rid of the yogurt, then filled the empty container with white glue and sealed it up again. After lunch, the unsuspecting colleague opened his yogurt, sniffed a spoonful and declared, “y’know, Phil, this yogurt really smells a bit ‘off.’” I forget exactly, but I think he may have tasted it just to be sure…

 

I have vowed never to let Phil within a few metres of the fruit juice that I take to work…

Just came across this rather scary titbit. I have never used a mouthwash (phew! relief!), but those who use an alcohol-based one on a regular basis would be well-advised to read this Telegraph UK article: http://tinyurl.com/8uwlsh

(Acetaldehyde, by the way, is the chemical that causes hangovers, see: http://en.wikipedia.org/wiki/Acetaldehyde)

Well, actually, it’s not an amphitheatre. This morning Stefano and I went to visit the Roman theatre in Fiesole, an ancient hillside town that offers a spectacular view of Florence on a clear day…not today, though…today was very hazy…oh well.

Stefano had (incredibly!) never been inside the archaelogical park in Fiesole, and I hadn’t been there since liceo (high school), so it was fun and new for both of us.

The 3000-seat theatre, built in the year 80 BC, still hosts concerts and art exhibits and so on. It’s worth a visit, for sure. Here are a few of the photos I took.

First, a panoramic shot of the amphitheatre. The second photo shows a view of the archaeological area seen from the arches of the Roman baths. You can make out the bell tower of the Cathedral of Fiesole beyond the arch on the left. The third photo offers a view of what is left of the Etruscan and Roman temples. 

Ah yes, a lovely day.

Stefano and I spent our August 2008 holiday in Bourgogne, France. We had a wonderful time there, visiting quaint Medieval villages, picking and eating blackberries on country lanes, drinking lovely pinot noirs and chardonnays and enjoying the region’s rich selection of cheeses and foie gras…now wait a sec…FOIE GRAS? Impossible, no, not Margaret the animal lover. She wouldn’t!

Well, uhm, in fact, er…she did.

I confess: I ate some foie gras last August for the first time in my life. We bought a terrine from a small local producer at a colorful street fair in one of those quaint villages. Yes, I know how foie gras is made…I know. I know! I don’t think I could have felt guiltier if I had tasted some roast puffin…gee wiz. Guilt, guilt, guilt.

Why am I writing about this today? Why in the world am I fessing up to eating a bit of foie gras…several months ago? Well, because I just finished reading this Science Daily article and am still in shock: http://tinyurl.com/af9wnr Eeeek!

This excerpt is particularly horrifying: “Stressed poultry birds are known to undergo spontaneous amyloidosis due to a chronic inflammatory response that causes amyloid fibrils to form non-functioning deposits of this protein-like material in their organs.”  Spontaneous amyloidosis???  

Pâté de foie gras is apparently the only type of “food” that contains “high levels of amyloid fibrils and no demonstration of it affecting people has been seen.” Still…no more foie gras for us. Never ever again. For many MANY reasons…