A first-year medical student at the LSU Health Sciences Center at the Shreveport School of Medicine won the American Society of Hematology (ASH) Trainee Research Award for “excellence in cancer research.” His project at LSUHSC-S “will focus on chemoprevention of head and neck cancers with curcumin.” I found this titbit in the June 8 issue of the Shreveport Times: http://tinyurl.com/2a7nfp
Could the tide finally be turning?
From a close MM listserv friend (thanks!!!):
A cat dies and goes to Heaven. God meets him at the gate and says, “You have been a good cat all of these years. Anything you desire is yours, all you have to do is ask.”The cats says, “Well, I lived all my life with a poor family on a farm and had to sleep on hardwood floors.”
God says, “Say no more.” And instantly, a fluffy pillow appears.
A few days later, 6 mice are killed in a tragic accident and they go to Heaven. God meets them at the gate with the same offer that He made the cat. The mice said, “All our lives we’ve had to run. Cats, dogs and even women with brooms have chased us. If we could only have a pair of roller skates, we wouldn’t have to run anymore.”
God says, “Say no more.” And instantly, each mouse is fitted with a beautiful pair of tiny roller skates.
About a week later, God decides to check and see how the cat is doing. The cat is sound asleep on his new pillow. God gently wakes him and asks, “How are you doing? Are you happy here?”
The cat yawns and stretches and says, “Oh, I’ve never been happier in my life. And those Meals on Wheels you’ve been sending over are the best!”
I borrowed the first part of this post title from a CBS report (http://tinyurl.com/2crn7b) on the cholesterol-lowering effect of guggulsterone, extracted from the guggul tree’s gum resin. But cholesterol-lowering is perhaps the least important property of guggulsterone.
An MD Anderson research team has just published a study on this remarkable sap extract, see the June 2007 issue of Biochemical Pharmacology (the abstract can be read at: http://tinyurl.com/38jlon). Thanks to a close MM Italian friend (grazie, e ci vediamo domani, speriamo non piova!), I was able to read the full study. Guggulsterone is a plant polyphenol obtained from the gum resin of the Commiphora mukul tree (more familiarly known as the guggul tree, don’t you love that name? My original post title was “Google Guggul”! 😉 ). As with many other substances on my research list, this is not a new discovery. Guggulsterone has been used by Chinese and Ayurveda (ancient Indian healthcare system) medicine for centuries to treat a variety of disorders, including obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis
As always, my favourite part of a scientific study is the conclusion: Guggulsterone inhibited the proliferation of human leukemia, head and neck carcinoma, multiple myeloma, lung carcinoma, melanoma, breast carcinoma, and ovarian cancer cell lines in a dose-dependent manner. It also blocked the proliferation of dexamethasone-resistant MM1 cells and doxorubicin-resistant breast cancer cells, and inhibited the villainous COX-2. I could dance with joy! But there is more good news.
The study also indicates that, because of lack of any known toxicity, guggulsterone should be further explored for its anticancer potential. Whether the concentrations used in our studies can be achieved in vivo, is unclear at present. [ ] Overall, our results indicate that guggulsterone inhibits the growth of wide variety of cells and induces apoptosis through downregulation of antiapoptotic gene products, modulation of cell cycle proteins, activation of caspases, inhibition of Akt and activation of JNK. As usual, the big problems are bioavailability and dosage, and, of course, testing in clinical trials.
A 2004 study (MD Anderson, again!) shows that guggulsterone suppresses NF-kB and NF-kB-regulated gene products, which may explain its anti-inflammatory activities. See: http://tinyurl.com/2w4buj And remember my post on curcumin, osteoclasts and bone resorption? Well, a 2006 study (http://tinyurl.com/2oa8zk) by the fabulous MD Anderson researchers confirms that guggulsterone is another substance that suppresses RANKL and tumor cell €”induced osteoclastogenesis by suppressing the activation of NF-kB. Ayurvedic medicine, by the way, has used guggulsterone for centuries to treat bone fractures and ostheoarthritis. So it comes as no surprise that this particular study shows that guggulsterone suppressed osteoclastogenesis induced by MM. More dancing!
So, let’s see: here we have a non toxic substance that has been used in traditional medicine for hundreds, perhaps thousands, of years and that has been shown to work against MM, osteoclastogenesis, COX-2, NF-kB, etc. Well, it certainly doesn’t take a genius to figure out that more research needs to be conducted on this and many other non toxic substances.
Let’s get the research ball rolling!
Well, it’s official. Last night I called my parents and told them we had decided to adopt another cat. I figured I would get a lecture on how we have too many cats already, how I am allergic to cats (true!), etc. But Mom just laughed and said Sweetheart, we already KNEW you were going to adopt one of those kittens! They know me well. 😉 She surprised me even more by adding Why don’t you adopt TWO of the kittens, so it won’t be so traumatic for them to be separated from their mother? She wasn’t kidding, either. I wish we could take them all!
Now that the adoption is official, I can post a photo of our baby. 
The kitten, the cream-coloured one in the photo (currently about the size of my boy Piccolo’s head!), will be joining our family once it is weaned, the first week or so of July. Perhaps with a sibling 😉 We don’t yet know if it’s a boy or a girl, but it doesn’t matter. We wish to continue the P name tradition (Puzzola, Piccolo and Priscilla), so if you can think of any good P-starting cat names, please let me know. If it’s a boy, I would like to call it Pronto, which is the Italian equivalent of hello? when answering the phone. It has other meanings, too: ready, prompt, quick, etc. After visiting Italy, a MM listserv friend called one of her cats Pronto, and I just loved the name! If it’s a girl well, we don’t have a name, yet. My brother in law suggested Paloma, which I like a lot. But we are still open to suggestions.
This is turning into a cat blog (!), but I AM also doing some serious research and will post about that soon!
I watched the most amazing (beautiful, in my opinion) video the other day. I don’t even remember how I found it, but here is the link (make sure the volume on your computer is turned on):
http://www.youtube.com/watch?v=nUDIoN-_Hxs
Enjoy!
Yesterday I came upon a recent study on curcumin and immune disorders. Published in the June 2007 edition of the “Journal of Biological Chemistry” (http://tinyurl.com/3yqzc6), it is titled Curcumin Prevents Tumor-induced T Cell Apoptosis through Stat-5a-mediated Bcl-2 Induction. Yes, I know, the second part of the title sounds nonsensical to non-scientific minds like mine. But when you read the abstract (and I am hoping to get my hands on the full text), it becomes clear that curcumin protects our T-cells. Indeed, this study shows that it restores T-cells from tumour-induced apoptosis: Administration of curcumin to tumor-bearing animals resulted in restoration of progenitor, effecter, and circulating T cells. In other words, curcumin can REVERSE the damage, or some of the damage at least, done to our T-cells by cancer. Now, isn’t that fantastic news? The study concludes: Thus, these results raise the possibility of inclusion of curcumin in successful therapeutic regimens against cancer. No kidding!
An article published in “Cancer Research” in January 2007 (http://tinyurl.com/2yng6z) also looks at curcumin and immunity. Concluding remarks: Thus, our results suggest that unlike many other anticancer agents, curcumin is not only devoid of immunosuppressive effects but also acts as immunorestorer in tumor-bearing host. I am all in favour of restoring my immune system!
Actually, this is not news to me, since a few months ago Prof. Aggarwal kindly sent me a study that he co-authored on this very topic (see my page on Curcumin and the Immune System). However, it is comforting to read a bit of updated research confirming curcumin’s strong pro-immune activities. This can only be good news for those of us who have compromised immune systems or autoimmune disorders.
A MM listserv member posted some amusing patient reports (real ones!) yesterday, and inspired me to look up some more. Here are some of the ones she listed (thank you!):
The patient refused an autopsy.
Patient has left white blood cells at another hospital.
She has no rigors or shaking chills, but her husband states she was very hot in bed last night.
Patient has chest pain if she lies on her left side for over a year.
On the second day the knee was better, and on the third day it disappeared.
The patient is tearful and crying constantly. She also appears to be depressed.
The patient has been depressed since she began seeing me in 1993.
Discharge status: Alive but without permission.
Healthy appearing decrepit 69-year old male, mentally alert but forgetful.
Patient had waffles for breakfast and anorexia for lunch.
She is numb from her toes down.
In Richard Lederer’s “Fractured English” and “More Anguished English,” I found a few more gems:
She is quite hard of hearing. In fact, she can’t hear at all in the left eye.
Sinuses run in the family.
He was eating his tray so I didn’t examine him.
He has an allergy to asthma.
The patient is a three-year-old who has been vomiting off and on for twelve years.
My personal favourite: the patient was bitten by a bat as he walked down the street on his thumb. Hehe.
This morning I went to visit my neighbours, who have three newborn kittens and three 1.5 month-old kittens (two different mothers, one of whom is my boy Piccolo’s mother). This is the cutest photo I took (of one of the 1.5 month-old kittens). Is cat number four on the way? 😉 My neighbours, of course, are urging me to take all their kittens! (They already have eight cats, two dogs and two turtles…)
Have a great weekend, everyone!
Puzzola showed up on our doorstep in September of 2001, almost as soon as we had moved into our home on the outskirts of Florence. She was skin and bones. Mostly bones. She was probably four or five months old at the time. Our cat-loving neighbours and I started feeding this affectionate little creature, who was clearly not a stray but had lived the first few months of her life with a family that had then abandoned her in our neighbourhood. Every time we went outside, there she was, our faithful little Puzzola, ready for some food, but also for love and caresses. Whenever we opened the front door, she would zoom inside, and we would have to rush after her and gently put her back outside. Until one day. She came inside and has stayed with us ever since. See, at the time we didn’t want another cat. We already had a cat, my Canadian cat, Keshé, whom I had gotten at a cat shelter in Toronto (unfortunately, she died of renal failure about six months after she arrived from the States, where she had been living with my parents until we got more settled here). But Puzzola was very insistent, and we had fallen in love with her, so it was just a matter of time.
Her name has a couple of meanings in Italian. In the beginning, the “aroma” emanating from her droppings in the litter box would send us scampering for shelter. I am not kidding. So the first meaning is: skunk (I happen to think skunks are gorgeous creatures, by the way). Puzzola is also the common Italian name for “marigold.” And our green-eyed Puzzola is most certainly a lovely flower, as well as the sweetest cat I have ever had.
One of the funniest and most remarkable things she does is to sit on our lar
ge farmhouse dining room table while we eat dinner. In the beginning, it was a bit disconcerting. Now we are used to it. As soon as I finish eating and push away my plate, I raise my hand, and that is her signal. She gets up, walks across the table and climbs into my lap, purring and kneading. But the amazing thing is, she won’t budge from her spot in the corner of the table until I let her know it’s okay. If Piccolo or Priscilla get on the table mamma mia, forget it. They MAY begin by sitting down at the end of the table, looking deceptively innocent, but they will begin inching closer and closer to our plates, trying to get their silly noses in our food. So they are not really allowed on the table. (Well ) [In this photo, by the way, Puzzola is pointing out the benefits of pure resveratrol 😉 ]
Even though Puzzola gets into my lap after dinner, she is definitely my husband’s cat. She worships him (perfectly understandable). Almost every evening, especially if he is late, she waits by the front door, listening. She gets very agitated when she hears his car approaching, starts meowing and stretching upwards, as though wanting to open the door for him. She doesn’t sleep with us. Our bed is too crowded for her, with the two youngest cats on it. She also doesn’t really play. I don’t think Puzzola played much as a kitten, unlike the other two. She had to scavenge for a living until she chose us as adoptive parents. So she just sits and watches Piccolo and Priscilla roll about on the floor. If they try to involve her in their fun, she runs up to the attic. She has dignity. She is our queen.
How’s that for a catchy headline? 😉 Except in THIS case, the headline actually comes closer to the truth than those ridiculous headlines screeching about multivitamins causing prostate cancer (see my recent post and page on that study).
Without Dr. Benelli’s books (see my Natural COX-2 inhibitors post), I might not have discovered the anti-MM effects of baicalein, one of the main compounds found in Scutellaria baicalensis, also known as Chinese skullcap. In spite of its scary-sounding name, which derives from the peculiar shape of its seed heads, this plant is actually a very friendly member of the mint family (Laminaceae). This online photo shows off its very pretty flowers (in fact, I am thinking of getting one for my back yard): http://tinyurl.com/29cp3f Its yellow root has been (and IS) used in traditional Chinese medicine for the past 2000 years to treat various ailments ranging from irritability (!) to hepatitis. Its healing properties are too many to be listed here, but can be found on many websites. I would just like to mention that it has anti-inflammatory, antioxidant, antitumour, antimicrobial, antifungal, antiviral, free-radical-scavenging €”okay, enough, enough, this is turning into a laundry list! €”properties. And more!
Baicalein and MM. Drum roll, please! A 2005 study published in Blood is titled: Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells (http://tinyurl.com/2jnlej) Suppression of proliferation? Induction of apoptosis in MM cells? Hurray! Scutellaria radix is the dried root of Scutellaria baicalensis (baicalensis, by the way, derives from Lake Baikal, in Siberia, where the plant was first discovered), which is an ingredient in HLJDT, a traditional Chinese medicine. It was found to have anticancer, antiviral, anti-inflammatory and antibacterial properties. Researchers tested its three main components–baicalein, baicalin, and wogonin–separately, and concluded that baicalein had the strongest anti-MM effects. In particular, it inhibited the proliferation of myeloma cell lines and the survival of primary myeloma cells, especially MPC-1- immature myeloma cells, and induced apoptosis in myeloma cell lines via a mitochondria-mediated pathway by reducing mitochondrial membrane potential and activating caspase-9 and caspase-3. Researchers also found that the antiproliferative effect of baicalein is not specific to myeloma cells, since it has also been examined for a human myeloid cell line, HL-60. I have already mentioned these HL-60 cells (see the link to the 2007 University of Pittsburgh study in yesterday’s post). Baicalein also inhibits COX-2, which may occur via the down-regulation of NF-kB. The good news continues: baicalein and Scutellaria radix also have an effect on the infamous IL-6. Yahoo!
Furthermore, baicalein is a potent inhibitor for -glucosidase, which catalyzes the final step in the digestion of carbohydrates. Based on these observations, we cannot exclude the possibility that the baicalein-induced inhibition of myeloma cell proliferation and induction of apoptosis result from not only the down-regulation of NF-kB activity but also various other actions of baicalein. So baicalein will kill my MM cells using different mechanisms AND reduce the impact of my dinner pasta carbs on my blood sugar at the same time. Now, that’s what I call a find! 😉 The study concludes: The results presented here clearly show that baicalein (or Scutellaria radix) can directly inhibit the proliferation of myeloma cells and present enough evidence for clinical trials to treat multiple myeloma. Indeed! Unfortunately, I was unable to find any clinical trials listed for Scutellaria, except for a Phase I/II trial (http://tinyurl.com/2oyohu) that is testing Scutellaria barbata D. Don, or barbed skullcap (a relative of our Scutellaria baicalensis), for advanced metastatic breast cancer. See this BBC News report: http://tinyurl.com/2vbf9u I mention this report mainly because I loved (and borrowed, thank you!) the headline: Mint leaf starves cancer to death ! 😉
Other studies. A 2003 study (http://tinyurl.com/2zt9bt) examines the effect of baicalein on the central nervous system, concluding that it has neuroprotective effects. And Scutellaria baicalensis was tested in head and neck squamous cell carcinoma (HNSCC), which is resistant to chemotherapy, in vitro and in vivo (http://tinyurl.com/262awe). The study concludes that Scutellaria baicalensis appears to have many anti-cancer mechanisms. If you are squeamish, do not click on this link, which posts the photo of a mouse with huge tumours. I was horrified. I know, I know. Also, here is a prostate cancer and baicalein study: http://tinyurl.com/yvggld I will stop here.
Concluding remarks on Scutellaria and MM. An April 2007 study (http://tinyurl.com/3xcwjw) confirms that Scutellaria baicalensis and baicalein (in particular) have anti-proliferative and apoptotic activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines. Another recently published study (http://tinyurl.com/2useyn) shows that baicalein combined with Dexamethasone suppress the growth of MM cells. Researchers report that this combination also reduced the expression of IL-6, as we have seen. The study states that the cooperative growth suppression of Dex and baicalein in myeloma cells might be useful for myeloma therapy. Combinatory treatment with both may overcome the Dex resistance and the baicalein resistance in primary myeloma cells, as well as myeloma cell lines. Good news for those MMers undergoing chemotherapy.
Where are those baicalein-MM clinical trials???
(from: http://tinyurl.com/ypxgj5)
Last week, looking up studies on ellagic acid and cancer, an endless task! (just to give an idea: PubMed has more than 700 entries for ellagic acid, and 129 for ellagic acid and cancer !), I stumbled upon anthocyanins (try to pronounce that!), which are flavonoids whose main purpose is to give colour to most flowers and fruit. According to Wikipedia, they are water-soluble vacuolar flavonoid pigments that appear red to blue, according to pH. They are synthesized by organisms of the plant kingdom and bacteria, and have been observed to occur in all tissues of higher plants, providing color in leaves, stems, roots, flowers, and fruits.
These pigments are mostly found in blackberries, blueberries, strawberries, elderberries, grapes and plums, as reported by The Columbus Dispatch: http://tinyurl.com/ypxgj5 The darker the fruit, the more anthocyanins it has. In plants, anthocyanins act as a sunscreen, absorbing high-frequency blue-green light. As antioxidants, they scavenge free radicals that form in plant tissue through ultraviolet radiation. Fascinating. And there is more: Anthocyanins appear to work by inhibiting compounds that weaken the immune system and stimulate tissue inflammation. They also seek out and destroy harmful free-radical molecules that circulate in the body, attack cells and cause aging, heart disease and cancer. Exactly how they do this, however, remains a mystery. University of Pittsburgh research has shown that a form of anthocyanin called cyanidin-3-rutinoside is a strong antioxidant and is similar to compounds called polyphenols, which are found in green tea. And it causes cancer cells to break down. The Pittsburgh scientists found that cyanidin-3-rutinoside caused potent oxidants called peroxides to accumulate and kill leukemia cells. Anthocyanins appear particularly useful for people who have had cancer surgery and are at risk of recurrence. Now how about that?
The 2007 study cited in the Columbus Dispatch can be read at: http://tinyurl.com/yozmkd Researchers added the above-mentioned cyanidin-3-rutinoside to several leukaemia and lymphoma cell lines, and found that it induced apoptosis in the malignant cells without affecting normal cells. Aha! The abstract concludes: These results indicate that cyanidin-3-rutinoside has the potential to be used in leukemia therapy with the advantages of being widely available and selective against tumors.
A 2004 study (http://tinyurl.com/25ewmn) shows that the anti-cancer (apoptotic!) and anti-inflammatory properties of anthocyanidins work at a molecular level. They are chemopreventive based on the: (i) inhibition of anthocyanidins in cell transformation through targeting mitogen-activated protein kinase (MAPK) pathway and activator protein 1 (AP-1) factor; (ii) suppression of anthocyanidins in inflammation and carcinogenesis through targeting nuclear factor kappa B (NF-κB) pathway and cyclooxygenase 2 (COX-2) gene; (iii) apoptotic induction of cancer cells by anthocyanidins through reactive oxygen species (ROS) / c-Jun NH2-terminal kinase (JNK)-mediated caspase activation. Now, let me see. COX-2, NF-kB, ROS, kinases haven’t I heard those mentioned somewhere? 😉
For an excellent overview of anthocyanins, see http://tinyurl.com/ywckdk. Anthocyanin isolates and anthocyanin-rich mixtures of bioflavonoids may provide protection from DNA cleavage, estrogenic activity (altering development of hormone-dependent disease symptoms), enzyme inhibition, boosting production of cytokines (thus regulating immune responses), anti-inflammatory activity, lipid peroxidation, decreasing capillary permeability and fragility, and membrane strengthening. This is a very interesting comprehensive study, and I cannot possibly summarize it properly. Among other things, it examines how anthocyanins protect from cardiovascular disease and pancreatic disorders, can perhaps help prevent diabetes and obesity, enhance memory and modulate cognitive and motor function, and defend our lungs against pleurisy and inflammation in general. Wow! This fascinating study also discusses bioavailability issues, which are part of the anthocyanin enigma, i.e., what happens after we swallow these pigments.
Another 2004 study (http://tinyurl.com/2aa8x4) informs us that anthocyanins have been part of the human diet for centuries, and have been used by Native Americans, Europeans and Chinese to treat hypertension, pyrexia, liver disorders, dysentery and diarrhoea, urinary problems including kidney stones and urinary tract infections, and the common cold. Recent studies have shown, among other things, that they protect against liver injuries, lower blood pressure, improve eyesight, have strong anti-inflammatory and antimicrobial activities, and suppress the proliferation of human cancer cells. This study also raises a few pertinent questions. For instance, how do anthocyanins provide all these health benefits: on their own, or by interacting with other phenolic compounds? What happens to anthocyanin molecules after ingestion? Reports on bioavailability of anthocyanins indicate that less than 1% of consumed anthocyanins is detectable in human plasma and urine. Okay, so clearly more studies are needed. But the potential is there. In the meantime, I am going outside to munch on some colourful flowers and fruits. 😉
A few studies: Leukaemia cells and a Hibiscus anthocyanin: http://tinyurl.com/2uhfw2; Lung cancer and anthocyanins: http://tinyurl.com/3bmlkl; Colon cancer prevention and anthocyanins: http://tinyurl.com/2eld4c; see also http://tinyurl.com/2xl3go; Cranberries and cancer; interesting study that examines colon, oral and prostate cancer cell lines: http://tinyurl.com/283k7k; Retinal disorders and anthocyanins (bilberry extract): http://tinyurl.com/279gu2; Heart disease and anthocyanins (elderberry extract): http://tinyurl.com/2xjs4d