Gambogic Acid and Cancer

Post number two of the day. A good friend (grazie!) recently sent me a study on gambogic acid (GA) published in the August 2007 issue of Blood (the abstract can be viewed at http://tinyurl.com/2xjgjm). GA is a naturally occurring brownish-to-orange resin called gamboge, which is derived from Garcinia hanburyi, a tree that grows in Southeast Asia. And in fact, this resin has been used in traditional folk medicine for a long time. Sound familiar? Yep. The purpose of the Blood study was to see if GA would suppress the infamous NF-kB. And guess what? It does. My favourite word appears again in this study: apoptosis. The study, which I would be happy to forward upon request, is full of scientific jargon, but the conclusion is clear: GA suppressed TNF-induced expression of cyclin D1, COX-2, and c-Myc, all linked to cell proliferation. [ ] We also clearly provided evidence supporting GA’s ability to potentiate apoptosis induced by TNF, 5-flourouracil (5-FU) and doxorubicin, with effects similar to those reported in tests of a specific inhibitor of NF-κB 21. Overall, our results provided the molecular basis for GA’s antiproliferative and anti-inflammatory effects. So GA can also be used to increase the effectiveness of some chemotherapy drugs. Good to know. There are several studies on GA and cancer, but apart from the above-mentioned one, the first that caught my attention, published in 2004, dealt with the effects of GA on human gastric carcinoma cells: http://tinyurl.com/2potff Remember Bax and Bcl-2? (see my recent Survivin MM with Curcumin post) Well, GA activated Bax and decreased the levels of Bcl-2 in these cancerous cells, a process which may contribute to the apoptosis mechanism. Interesting. Furthermore, GA was found to target malignant cells, not normal ones. Also very interesting. This is confirmed by a study (http://tinyurl.com/ynuc39), published in August 2007, that looks at the apoptotic effects of GA on human hepatoma cells: GA selectively attacks tumour cells, leaving normal ones alone. Another study published in May 2007 (http://tinyurl.com/39ju89) shows that a derivative of GA, called NG-18, markedly induced leukemia HL-60 cells apoptosis. And once again, we read that Bcl-2 was downregulated and Bax was upregulated.

I will stop here, even though there would be a few more studies to discuss. The important conclusion is that here we have yet another non toxic substance that possesses the remarkable ability of distinguishing between healthy and cancer cells. This astonishing fact never ceases to amaze me, even though the above-mentioned Blood study informs us that between 1980 and 2000, as many as 70% of all drugs approved by the U.S. Food and Drug Administration to treat cancer were based on natural sources. How about THAT?!!!

Vet Visit

Two posts today. First, an update on Puzzola, my seven-year-old cat. My Mom and I took her to the vet yesterday. The upshot is that she does not have kidney stones (phew!), but she does have some small mineral deposits and crystals in her kidneys and bladder, so she will have to be on a special diet and be monitored closely for months. However, the situation is not serious, and we were reassured that she will be okay. Since her last couple of visits to the vet have not been fun at all (!), she scampered away from me when I went to get her to take her to the vet (how do they know???), and I ended up chasing her all over the house, which was not fun for either of us. When I finally cornered and grabbed her, she peed all over me, absolutely terrified. I wish I could have explained to her that I was doing it for her own good! Oh well. However, I must say that when the vet rolled her over on her back, and we held her paws for the ultrasound, she didn’t move an inch, not even when her tummy was shaved. My brave girl!

Drinking from the Faucet

Priscilla and tap waterOur two-year-old cat, Priscilla, has learned a new trick €”drinking water from the faucet. Now, I know that heaps of cats do adorable things like that, but I have never had a cat who is so totally OBSESSED with drinking water in this manner. Whenever someone heads in the general direction of the bathroom, she rushes ahead, leading the way over to the sink. And she won’t let you go about your business until she has quenched her thirst. Thirst? What thirst?!!! She must drink ten times her body weight in tap water a day! (Ok, SLIGHT exaggeration…) Anyway, today I have a ton of errands to run, including taking my eldest cat Puzzola to the vet for an ultrasound (she probably has kidney stones, poor sweetie), so I don’t have time to do any research, but I thought I would post this photo. My research can wait till tomorrow. 🙂

More Ramblings and Circus Update

In yesterday’s post I should have specified that I discussed my JUNE test results with my doctor. I haven’t had any tests done since then. In Italy, patients see their test results before their doctors do. In fact, I have my test results mailed to me (and it’s a free service, too!). You can also go pick them up at the hospital. And we patients keep all of our lab reports, including X-rays. As I recall, in the U.S. and Canada it’s the complete opposite: you have to go to your doctor’s office to see and discuss your test results. That’s what I had to do, at any rate, when I lived in Massachusetts and Ontario.

I have always debated whether or not to answer blog comments publicly in my comment section, or privately, via individual e-mails. I have done both, but mainly the latter. Today I wanted to address one of the comments publicly: why am I testing curcumin without bioperine? Excellent question, to which I have two answers: 1. the capsules without bioperine are available on the Italian market, whereas I have to order the capsules WITH bioperine from the U.S. (a real drag, for many reasons), and 2. I simply wanted to see if curcumin capsules without bioperine would work as well as the ones with bioperine. Here follows the history of my curcumin intake, in a nutshell: in 2006, for months I mixed curcumin C3 powder with a fat (warm coconut milk, flaxseed oil, etc.); last summer, while on holiday in the States, as a matter of convenience, I took curcumin C3 capsules with bioperine; last fall I decided to continue to test those capsules, and then this summer I decided to try curcumin C3 capsules without bioperine. My test results have been quite decent up to now, except for a brief period last fall when I took a half dose of curcumin by mistake, duh. So, if my next blood test results are good, I would prefer to take the bioperine-less capsules from now on. Easy peasy!, as Jamie Oliver (the Naked Chef) always says. 😉

Ah, speaking of tests, I did not go to the hospital to have my blood drawn this morning. I decided to wait for a another couple of days after I woke up with a very bad headache (of course, it was gone by the time I had finished my morning coffee, sigh). Tomorrow I will be very busy, but I may have time to go to the lab on Friday.Peekaboo, August 2007

Feline circus update. Peekaboo is now beginning to chase playfully after our three older cats, who are besides themselves with a mixture of fury and bewilderment. The little darling just wants to play with them, but they see matters differently. So all you can hear in our house these days is HISSSSS GROWWWWWL GRRRRR SNARRRL HISSSSS! I have also seen a few paws raised but €”in all honesty €”I cannot blame the older ones for wanting to whack the little critter, as adorable as she is (in the photo she is sitting on my dining room chair, planning her next move). She is simply…too much! This morning she began chasing after and playing with Piccolo’s tail! The poor guy tries to retain some dignity by remaining on high surfaces where she can’t reach him (yet), so he will jump from our dining room table to the kitchen counter and so on. If I didn’t feel so sorry for my adult cats, I would find it all very amusing. Well, I have a bit of research to do, the cats are asleep, all is peaceful at the moment…so off I go! 😉

Diet Ramblings

Today I realized that I should be concentrating more on my diet. During my recent southern Italian holiday, I was eating more (a lot more!) than I usually do at home, even though, oddly enough, I did not gain any weight. In fact, if anything, I lost a bit of weight. In addition to eating two and three course meals, though, I was eating foods that are not really (!) part of a cancer diet, such as sausage (oh, so yummy, though!). In my experience, southern Italian cooking is not the lightest fare on Earth. Delicious, but not light. For instance, the eggplant parmesan that Stefano’s cousin prepared for our August 15 ferragosto feast was absolutely divine, but she made it the traditional way, that is, fried not just once but TWICE. No, I am not kidding. The first frying occurs after you get rid of the eggplant’s bitter taste (by sprinkling a bit of coarse sea salt on the slices which then are placed inside a colander to drip for about an hour). You then roll the fried slices in flour, dip them in egg and fry €˜em…again. The final part coincides more or less with what we all know about this dish: layers of eggplant, tomato sauce, fresh basil and mozzarella and other kinds of cheese. Yummy, but wow! After many of those rich meals, I barely had the strength to crawl upstairs and take a long nap. Plus, when Stefano and his relatives learned that my iron stores (my June test results) were very very low, they almost began force-feeding me red meat every day. Help! I have always been a wannabe vegetarian and still stubbornly refuse to eat some kinds of meat (rabbit etc.), but I also know that we absorb less iron from vegetables (non-heme iron). I tried to point out that my serum iron is well within the normal range, it’s just my ferritin that is low, but to no avail. I was outnumbered. 😉 In the end I stopped protesting and ate the bloody meat. One good thing about eating meat in Italy is that it is safe. No hormones, no antibiotics, etc.

On a related note, I went to see my doctor’s substitute this morning. After we happily discussed my most recent test results, she printed out the request for my next set of blood tests, so I may go up to the Careggi hospital lab to have my blood drawn tomorrow morning. That way I can see what effect a heavy southern Italian diet coupled with bioperine-less curcumin capsules had on me. Should be interesting.

On another related note, one of the newsletters that I subscribe to is Dr. Andrew Weil’s Daily Tip. Today’s tip, which actually gave me the idea for this post, is titled Four Ways to Reduce Inflammation, since inflammation is linked to many nasty ailments, including cancer. (In fact, I have a few notes on the cancer and inflammation link in my “blog ideas” folder. For a future post.) At any rate, these are Dr. Weil’s recommendations:

1. Eat a diet rich in omega-3s, including wild Alaskan salmon, sardines, freshly ground flaxseed and walnuts. 2. Incorporate plenty of fresh, organic fruits and vegetables in your meals. 3. Reduce your intake of polyunsaturated vegetable oils (such as sunflower, corn and safflower oils), replacing them instead with extra-virgin olive oil. 4. Use healing spices in your cooking: turmeric, ginger and red pepper can add zing to meals and are all natural anti-inflammatories.

Makes sense. I already follow many of these suggestions, as well as a few of my own. My biggest downfall, as I have written in previous posts, is chocolate oh, and wonderful rich chocolate and nut ice-cream during the summer. Have I ever mentioned that we happen to live practically around the corner from the best ice-cream parlour in Florence? Ah yes. How coincidental is THAT? 😉

Survivin MM with Curcumin

Nope, survivin is not a typo. A new study, published in the August issue of the Journal of Experimental Hematology (Chinese Association of Pathophysiology), examines the effects that curcumin had on a human (peripheral blood) MM cell line: RPMI 8226. The results are interesting but hardly surprising. One word says it all: apoptosis! Curcumin, in fact, was found to down-regulate survivin (there’s that word, again!) and Bcl-2 mRNA, and to up-regulate Bax mRNA. Hmmm, what are these three items? Survivin is a member of the inhibitor of apoptosis protein (IAP) family. Not a nice family to have in your neighbourhood, I would say. 😉 A study published in February of 2007 (http://tinyurl.com/2s9xon) informs us that there is a significant correlation between survivin expression at protein level and clinical course of MM. Therefore, the down-regulation of survivin is good news for us MMers. As for Bcl-2, it’s an anti-apoptotic gene which may contribute to the chemoresistance of MM cells. In fact, MM cells that survive chemotherapy treatments show increased levels of this gene. See: http://tinyurl.com/3468dk So the down-regulation of Bcl-2 is also good news. And, finally, Bax is a protein that promotes apoptosis. Aaaah, apoptosis, which has become my favourite word in the English language ever since I was diagnosed with MM in 2005. Okay, back to us and the new curcumin-MM study. Unfortunately, since I do not have a reading knowledge of Chinese, I will not be able to comment on the full study. But the abstract, which can be found at http://tinyurl.com/2hh378, certainly adds a few more details to the story of how curcumin is able to kill MM cells.

I am slowly getting back to my normal routine after returning from our summer holiday, but introducing a funny, adorable but also rambunctious kitten into our household is taking more time and energy than I had predicted. Our three adult cats are still hissing and growling and being quite grumpy, but surprisingly this is having no negative effect on Peekaboo’s cheerful and positive attitude. What I cannot figure out is WHY she will happily bounce right up to their noses while they are growling and baring their fangs talk about tempting fate! I expect she will get whacked at some point, but so far that has not happened. Right now she is fast asleep right by my keyboard. Cutie pie. At any rate, I will continue to do research in my snippets of time (and try to answer the e-mails I have received, sorry for the delay!). And, ah yes, I have a couple of very promising new substances on my list! Time for lunch! 😉

Attacking Leukemic Stem Cells: Parthenolide

Today I read about a $1.7 million grant awarded to a team of scientists at the James P. Wilmot Cancer Center at the University of Rochester Medical Center for the development of new therapies attacking leukemic stem cells. And one of the substances under examination is parthenolide, which seems to be the first single agent that can attack leukemia at its roots. Hurray! A water-soluble form of parthenolide is expected to enter Phase I clinical trials later this year. I don’t have any time to pursue the topic any further today, but I will be watching it closely. And in the meantime I guess I will be ordering some parthenolide! Oh, this is very exciting!

Back From Holiday

Just a quick note before dinner: we got back from our holiday in southern Italy on Thursday, and have been busy busy busy (BUSY!) since then. Since our return, I haven’t had time to check my e-mail (so now I have about 200 messages to go through, argh!) or do any blogging. Plus, this is THE weekend that we are introducing Peekaboo to her new feline family. Peekaboo and the kitten in the mirror!Yep, vacation’s definitely over! Mamma mia! 😉 We have been careful to do these introductions properly and slowly, BUT there still has been a lot of hissing and growling and stress on the part of our three adult cats. Can’t blame them. They see the little critter as a threat, and are very upset. On a positive note, though, they are not attacking her. They simply hiss and growl and bare their teeth at her whenever they set eyes on her. And when little Peekaboo gets too close for comfort, they growl more loudly or, if that doesn’t work (it doesn’t…the little imp isn’t scared at all!), they scamper up to the attic to hide. Hmmm. Frightened of a teeny TINY kitten? Sigh. Needless to say, Stefano, my parents and I are simply exhausted from running up and down the stairs after little Peekaboo, who is tremendously excited to be out of confinement (in this photo, she is trying to attack the kitten in the mirror… 🙂 Her eyes are still blue and will remain blue, by the way, too bad the flash interfered with the colour, here) and is dashing hither and thither. Tonight in order to give our adult cats a rest and time to mull things over, we will shut Peekaboo in her room again. Actually, we all need a rest! But tomorrow her door is going to be opened for good. We will let the four cats figure things out on their own. Tomorrow. 😉

Herculaneum/Ercolano

Ercolano, veduta mare, 2007Yesterday we visited Herculaneum (near Naples), located at the foot of the Vesuvius. Most of what follows is taken from bits and pieces I found on the Internet, in my memory and in the information booklet that you get when you purchase entry tickets to the ruins. In past blog pieces, I forgot to mention that almost certainly the eruption that destroyed Pompeii and Herculaneum did not occur in August but in November of 79 A.D., according to the previously-mentioned documentary ( Superquark ) that I watched recently on Italian TV. Now, this may not seem like a big deal or the most fascinating bit of news you have ever read, but the documentary presented clues and evidence in such a brilliant manner that I was reminded of CSI Crime Scene. It reported that ancient transcriptions of the eruption date were simply wrong, and that an error probably made by one transcriber was simply copied over and over again. This new theory is based on recent archaeological finds in Pompeii. I remember three of the main pieces of evidence presented. House of the Relief of Telephus, Herculaneum 2007

1. Sealed clay wine containers with traces of the wine that had been produced that year were found in Pompeii. This would prove beyond doubt that the grape harvest had already taken place, i.e., BEFORE the eruption. There is no way that the grape harvest of 79 A.D. could have taken place before the month of August. 2. The inhabitants of Herculaneum were found clad in (bits of) heavier clothing than what would be expected in the hot month of August. 3. But perhaps the most important find was a coin that couldn’t possibly have been in the possession of one of the unfortunate city dwellers in the month of August, 79 A.D. I don’t remember the exact date on the coin, but that was quite a convincing piece of evidence. Anyway, I thought these were remarkable fragments of the Vesuvius eruption story. Ok, enough about erroneous dates. 😉

Some of the luxury homes of Herculaneum overlooked the Bay of Naples in ancient times. Now the sea is much farther than it would have been back then. If you look closely at the panoramic photo (top of post), you can make out the sea in the background.

During the eruption of 79 A.D., Decumano Massimo, Ercolano 2007Herculaneum was covered by about 20 meters (about 65 feet) of pyroclastic material €”water, ash and debris €”that solidified into volcanic tuff, forming a sort of airtight seal around the city. Herculaneum was thus almost perfectly preserved for centuries until it was discovered by accident in 1702 by workers digging a well in an orchard. Until then, Herculaneum had simply disappeared off the face of the Earth. The eruption, you see, had added an entire strip of land to the surrounding coastline, so the precise location of the ancient city had been lost. Actually, I think that it was very unfortunate that Herculaneum didn’t remain hidden until recent times. House of the Beautiful CourtyardHad the city been excavated with modern techniques, in fact, more of it would certainly have been preserved. In the 18th century and subsequent excavations, entire buildings were ransacked and damaged, frescoes were torn from walls, perishable goods and other organic matter were left to deteriorate etc. Concerning organic matter: unlike Pompeii, excavations in Herculaneum have unearthed plants, fabrics, furniture, and even parts of the ancient wooden house structures. This was made possible because the first phase of the eruption didn’t hit Herculaneum as forcefully as other sites (Pompeii and Stabiae, e.g.). And in fact Herculaneum still has several two-story buildings (see photo), unlike Pompeii, which suffered more structural damage (roofs caving in etc.).

When you compare the two cities, the first noticeable difference is size. Pompeii is huge (66 hectares, of which 15 still remain underground) whereas Herculaneum is much smaller: 4.5 hectares are visible, and as many as 20 may still be hidden under the modern city, including important public buildings, probably. Another big difference is that Pompeii is more removed from its modern counterpart and gives you much more of a feel for how ancient Roman city life used to be. Modern Ercolano, as can be seen in the photos I took yesterday, is instead precariously perched right above the ruins (see photo below).Herculaneum, the old and the new That reminds me: the first time I visited Herculaneum, I found the contrast between ancient and modern mesmerizing, but this time it really bothered me. I didn’t want to see modern laundry hanging out to dry practically over my head. I wanted to be completely immersed in my vision of how city life used to be two thousand years ago. But then I would look down and see that I was walking on ancient mosaic floors…

Wall paintingThe main problem of Herculaneum today is preservation and restoration. Apart from destructive and stupid vandalism (we saw and were outraged by the damage that had been done to walls and frescoes by imbeciles writing their names etc.), quite a lot of water damage has been done to the ruins by the modern city. Until these extremely difficult problems can be solved, it is best that the rest of ancient Herculaneum remain buried.

Pompeii, Part III

view of Pompeii, August 2007

Yep, yet another post on Pompeii. In fact, I took enough photos at Pompeii the other day to keep me posting for months. But seriously, this will probably be my last Pompeii post. Narcissus (wall painting), House of Loreius Tiburtinus, PompeiiI don’t want to overdo it. Tomorrow we are going to Herculaneum, which is less famous than Pompeii but in some ways more interesting. It too was destroyed in the eruption of 79 A.D. So my Herculaneum saga is about to begin. 😉

I took the above panoramic photo just as we were leaving Pompeii. At that point, my brain wanted to stay and explore the streets where we hadn’t been, but we were too exhausted even to contemplate such an effort. Here I was looking toward the theater (far end). The photo gives a vague idea of how vast Pompeii is. But if you want to be really overwhelmed, have a look at the map of Pompeii using Google Maps or Google Earth.

peristilio, casa degli amorini dorati, 2007This (left) is a view of the peristyle (an open colonnade encircling an internal garden) of the House of the Amorini Dorati, or Gilded Cupids, which received its name from the gilded flying cupids that at one time were part of its wall paintings and which are now preserved in the National Archaeological Museum in Naples (if you are in Naples, don’t miss visiting this museum, by the way). The house is very well-preserved and, I thought, one of the most striking (of the ones we saw on this trip, of course). The garden, by the way, displays its original marble decoration. We were lucky: this house had been shut for renovations for the past ten years and was reopened only last year.

Here is a typical street in Pompeii showing the stepping stone crosswalksstepping stones, Pompeii 2007 that city dwellers used in order to avoid stepping into the sewage that flowed through the city streets especially after a rainstorm. I learned from a recent fascinating documentary broadcast on Italian TV ( Superquark, for any Italians who read my blog) that Pompeii did not have a brilliant sewage system, unlike Herculaneum. These stepping stones are quite high, actually. Sensibly so, I guess! 😉 Besides being a bit on the narrow side, the sidewalks themselves are as high as the stones, more or less. I do not have a mathematical brain, so I have no idea how high, but I am sure this interesting little fact would be posted somewhere on the Internet. Hint: when visiting Pompeii, wear some sturdy footwear, since the ground can be uneven here and there, and in fact even these stepping stones are not flat. I slipped and almost fell on a couple of occasions. You really have to watch your step!

Gladiatorial barracks, Pompeii 2007