The importance of translocations

January 12, 2009 / / 5 Comments

Ever since I realized the implications of my MGUS and then SMM (well, to be precise, my 2005 bone marrow biopsy result talks about “multiple myeloma,” not “smoldering myeloma”…) diagnoses, I have been interested in studies about the progression of these two conditions to actively malignant myeloma.

A blog reader (thank you!) must have been reading my mind. He recently sent me a heap of studies dealing mainly with the issue of genetic codes in MGUS and myeloma, and that of the progression from MGUS to MM.

Even though it’s way too early to get into it all, one of these studies told me something that I didn’t know: chromosomal abnormalities, or translocations, occur in MGUS, too. So much for (my) believing that only myeloma folks developed wacky genes…At this point, though, I should reassure those with MGUS that a few abnormal chromosomes doesn’t mean that progression to myeloma is inevitable. Oh no, not at all. As I mentioned, though, it’s too early to get into it.

I just wanted to explain my silence, I guess. In the past couple of days I have been poring over piles of statistics, looking at graphs that make little or no sense to me, wading through discussions on translocations, not just those concerning the infamous chromosome 13 (deletion/non deletion), etc…and yes, I admit that it was all terribly overwhelming at first, but then I decided that I simply would try to understand what I possibly can…and set the rest aside, at least for the time being. After all, I cannot become an expert cytogeneticist overnight… As for posting a few words about these studies, well, I will give it a try. Soon, I hope.

In my free time, I have been following the interesting GMO (etc.) discussions on Fanatic Cook’s blog (I have a link here to her blog, just scroll down my Pages almost to the end). Among other items, she has a few interesting posts on genetically modified soy… I must say that I am full of admiration for this researcher, from whom I have learned so much…please visit her blog whenever you have a spare moment or two, you won’t regret it, I think. Here’s the general link: http://fanaticcook.blogspot.com/

In my next life, I want to be a marathon lounger

January 10, 2009 / / 2 Comments

Yesterday my niece sent me the link to a video titled “An engineer’s guide to cats.” Amusing, see: http://tinyurl.com/9olzw8 (the mystery of today’s post title is therein revealed…)

And then, as if I had nothing better to do yesterday, hah!, I began watching a few YouTube cat videos…couldn’t help it, too cute. And I found the following:

Scuba cat: http://tinyurl.com/9n7tok Quite an amazing story, but certainly something that I would never try with my own cats!:

How to break up a cat/kitten fight (hehe): http://tinyurl.com/2z5beb You have to watch the whole thing…this particular clip was featured on the Jay Leno show.

Here is a collage of funny or cute cat clips: http://tinyurl.com/633j6y I had already seen many of them, like the cat chasing the bear, but hadn’t seen the tiny black kitten falling asleep (oooh so cute!), the cat playing ping pong and the cat jumping on water…and how about the cat arranging itself inside a glass? Or the one squeezing itself out of a bottle?

Watching all these cute cat videos made me want to rush out and buy a video camera to take films of my own cats, whose antics are certainly comparable in funniness and cuteness…Priscilla, who loves to drink water from the bathroom tap (see photo) and cuddle under my sweater (luckily, only during the cold weather months!) with only her tail peeking out….Peekaboo and Piccolo, who answer all my questions with their own meaningful meows and peculiar trills and chirps (note: they ignore me if I don’t use the correct question intonation…)…Puzzola, who loves getting (or stuffing herself) inside cardboard boxes of any size. If it’s a small box, she will stick her head inside and pretend not to notice that the rest of her body is totally visible.

Oh, and Piccolo and Peekaboo bump their foreheads to mine (Piccolo gives me such forceful bumps sometimes that he makes me take a step backwards). And all the funny and acrobatic jumping and playing and fighting that goes on in our house, usually instigated by Peekaboo, the fearless imp (I should have known I was in for some serious “trouble” when I first set eyes on her, about one and a half years ago, see photo)…the list goes on…and on…

Happy Birthday to one of my dear blogging friends! You know who you are! 🙂

Genistein and signalling pathways

January 9, 2009 / / 4 Comments

Yesterday I went through the 2006 “International Journal of Cancer” study (abstract: http://tinyurl.com/7eady3), which discusses how genistein affects the transcription factor NF-kappaB and the Notch-1 signalling pathway in pancreatic cancer cells.

[Note 1: Notch signalling is crucial for the growth and survival of multiple myeloma cells, not just pancreatic cancer cells…see, for instance, these two “Blood” 2004 abstracts: http://tinyurl.com/9p7k5e and http://tinyurl.com/7f9vzw. So this discussion is relevant to us myeloma folks, too.]

The abstract informs us that Notch signalling helps maintain the balance between cell proliferation, differentiation and apoptosis, and thereby may contribute to the development of pancreatic cancer…this process is, however, blocked by genistein. And, by inhibiting Notch-1, genistein also blocks NF-kappaB, which mediates survival signals that inhibit apoptosis and promote cancer cell growth. This process also affects the genes controlled by NF-kappaB, as we will see in a sec.

The cancer cells have no way out…except death.

[Note 2: the implications of inhibiting the Notch/NF-kappaB signalling process gave another push to my idea of gathering in one place (say, an Excel spreadsheet) all the data I have collected in the past year or so…if only I had more free time, had a scientifically-oriented brain, and were more organized…eh. Well, my rambling all over the place will simply have to do for now. But I have to admit that even I get overwhelmed by all the info contained in my own blog!!! If I could condense it somehow…]

The full study begins with the usual cancer statistics…in this case, of course, those concerning pancreatic cancer, which has the worst prognosis among all major cancers. Apparently, though, people whose diets are high in soy are less likely to get this type of cancer, suggesting that a high intake of soy products may protect people against pancreatic cancer.

Basically, as anticipated in the abstract, the study demonstrates that the inhibition of Notch-1 blocks NF-kappaB, at least in part. And this process also hinders genes that are regulated by NF-kappaB, such as COX-2, cyclin D1, MMP-9, Bcl-2, Bcl-xL and survivin. Well, well, we meet again…these are all genes implicated in the survival and merrymaking of myeloma cells, so this is a very important point.

In conclusion, the study demonstrates that the administration of genistein leads to the death of pancreatic cancer cells. The researchers speculate that one possible mechanism by which genistein induces apoptosis is due to down-regulation of Notch-1, a gene that is abnormally activated in many human malignancies and keeps pancreatic cancer cells alive and well, as it does with other types of cancer cells (erythroleukemia and cervical cancer are mentioned here).

And, as we know from my December 29 post, genistein also kills myeloma cells AND increases bone formation…

Toxicity issues. I was actually somewhat reassured after perusing a report carried out by the National Toxicology Program (U.S. Dept of Health and Human Services) in 2006, see http://tinyurl.com/9voc22 Incidentally, it answers Chris’ question concerning chickpeas. Even though the main source of genistein is soy, much smaller amounts can also be found in Lentils, peas, kidney beans, peanuts, chickpeas, broccoli, cauliflower, and barley meal. The report concludes that genistein is safe for human (adult) consumption. In order to reach possibly harmful levels of genistein, we would have to swallow huge quantities of the stuff, more than 35 mg/kg a day. Yep, that’s a lot. In any event, the main potential toxicity has to do with reproductive issues, which is not a concern for me.

I also took a look at a more recent (=2008) NTP report (see: http://tinyurl.com/7z3gnd) that confirms that although genistein did show adverse effects with dietary exposures of 100 or 500 ppm, there were no clear adverse effects on the reproductive or developmental parameters measured at genistein concentrations ranging from less than 1 ppm (control diet) to 100 ppm, a range of doses producing serum concentrations achievable from the phytoestrogen content of human diets.

Well, the more I read, the more I am tempted to try genistein (only from a certified non-GMO source), but I have other things to test first…in the meantime, I will (try to) keep an eye on this substance, too…

Genistein and myeloma, part II

January 7, 2009 / / 4 Comments

A blogging friend sent me the full genistein study (thanks!!!) recently published in “Phytotherapy Research” (abstract: http://tinyurl.com/7wwnku), a study that I mentioned in my December 29th post. It starts out with the usual dismal information about multiple myeloma, which is a B-cell malignancy characterized by the latent accumulation in bone marrow of secretory plasma cells with a low proliferative index and an extended life span and accounts for 1% of all cancers and more than 10% of all blood cancers…oh, and it remains incurable…

There follows a description of what happens when the transcription factor NF-kappaB gets constitutively activated (that simply means that it is activated all the time)…this is not good, as far as we myeloma folks are concerned, since it means that our myeloma cells are protected from apoptosis (=from kicking the bucket). Reading on…blablablabla…okay, the upshot: NF-kappaB is an important target for myeloma treatment. So far, we have learned nothing new.

The research team chose to test genistein, a predominant isoflavone found in soybeans, which has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. Genistein suppresses NF-kappaB and many of the genes that it regulates. And humans can consume it safely, so they say.

Results. The team tested two different myeloma cell lines that expressed a hyperactive NF-kappaB. The cells were treated with different amounts of genistein and doxorubicin. A very small amount of genistein was sufficient to suppress the activation of NF-kappaB. It also worked synergistically with doxorubicin, leading to greater antitumor activity in vitro. Good.

For the more technically-oriented, genistein also inhibited Akt phosphorylation (when this happens, NF-kappaB doesn’t travel to the nucleus, which is a GOOD thing, take my word for it) and down-regulated ICAM-1, cyclin D, bcl-2 and bcl-xL (=four wicked genes).

Okay, but does genistein kill myeloma cells? Yes. How? Well, The precise molecular mechanism is not clear, the researchers admit. But wowie zowie, check this out: like curcumin, zerumbone and cyclopamine, genistein inhibits the Notch-1 pathway…does anyone remember what that pathway is? Right, it has to do with STEM cells…well, this might tip the balance in genistein’s favour, as far as I am concerned…yes, this is good news indeedie! I am so glad I read the full study!

Thanks to my big-hearted blogging friend, I have in my possession the 2006 genistein-Notch full study, which is next on my reading list…in the meantime, scribble scribble, a mental note: make more chickpea curries for dinner…

Margaret's Corner

Month: January 2009