Be happy, but not TOO happy…(oh, and my test results…)

January 31, 2008 / / 8 Comments

The first part of my post title refers to a Science Daily article I read this morning while waiting, or fidgeting is more like it!, to drive to the hospital to pick up my blood test results: these refer to the tests that Sherlock and I took before beginning our biocurcumax experiment. More precisely, to the November-January period of my CMC (cocoa mass curcumin) experiment, when I was also taking a low dose, no more than the daily recommended dose, of Scutellaria baicalensis and Zyflamend.

A quick aside: you can read this rather interesting Science Daily "happiness" article here: http://tinyurl.com/2l38re In a few words, a new study suggests that "moderate happiness may be preferable to full-fledged elation." The “don’t be too elated” study seems quite appropriate in view of my current test results: yep, more seesaw results. I am getting used to going a bit up then down, so it’s no big deal, now that I have had time, a few hours, to process and digest the numbers. Ready? Ok, here goes.

My IgG went up from 27,80 to 31,90 g/L. Now, that’s not a huge jump in the wrong direction, but it’s still a jump, 12% or so. However (!), my m-spike went down slightly, from 2,20 to 2,17, and my monoclonal component decreased from 25,7 to 25 %. These aren’t huge changes compared to my previous tests, but I think the two itsy bitsy decreases are interesting. From what I understand, in fact, the m-spike and IgG count go down together, hand in hand, and vice versa. Perhaps I was fighting a cold or some sort of infection during those two months, so my good immunoglobulins increased. It’s very possible. Well, I won’t say any more on the matter until I speak with my hematologist next Wednesday.

Ok, first let’s get the negative stuff out of the way:

Ferritin ( = iron stores) is back to 7, down from last test’s 10 ng/mL. No worries, it has been that low. It will go back up.

My albumin is down from 49,5 to 48,2 %. Oh well. It’s been lower.

Beta-2 microglobulin went up to 1,9 from 1,6 mg/L. Still way within normal range, though.

Hematocrit went down a bit, from 39,5 to 37,4 g/dL. Hmmm. Well, it, too, has been lower.

Now for the good stuff:

My serum iron jumped from 62 (barely within the normal range) to 81 microg/dL. Guess all those steaks and spinach with lemon juice made a difference, after all!

Bence Jones is negative. For the blog readers who are not members of the very exclusive Myeloma Club: that’s good.

Total protein went down a teeny bit, from 8,8 to 8,7, creeping back toward the normal range (high end of the normal range is 8,6 g/dL). Good.

LDH, or lactate dehydrogenase, decreased from 158 to 146 U/L. Also good, since high levels of the LDH enzyme are associated with aggressive disease, which we do not want!

Creatinine is stable at 0,7, no change.

Calcium went down from 9,6 to 9,2 mg/dL. Still way within the normal range. Nice to see it go down a fraction.

CRP is still within the normal range. I hate it that I don’t get a number but only a “less than” value.

Oh, I almost forgot. All of my celiac disease tests were negative, and you know what that means: pasta for lunch!

Well, even though I know that the myeloma is still stable (Sherlock, whose mind is much more analytical than mine, confirmed my feeling), I admit that I am not the happiest camper in the world right now. I would have liked to have seen a drop in my IgG count, a substantial drop. But it’s true that my m-spike dropped a wee bit, and besides, the above-mentioned happiness study shows that, compared to blissfully happy folks, people who are only mildly happy have room for improvement. I like that. Furthermore, if you are completely happy and satisfied, you have nothing to wish for, as Sherlock wisely pointed out to me earlier today. And that is no fun. So, hey, every so-so test result has a silver lining, isn’t that the saying?

My questions, for now:

1. Did the Scutellaria baicalensis clash with the curcumin cocoa mix, even though I took them at different times of the day?

2. Did I take enough Scutellaria to make a difference? (Off the top of my head: probably not.)

3. Do tests taken in certain periods of the year yield similar results? (Work in progress.)

4. When I am testing one supplement, should I quit taking curcumin for a month or so, to see if said supplement really works by itself? Now there is a scary thought. It’s like asking the Peanuts character Linus to give up his security blanket for a month or so. Tremble tremble ! But, in the interest of science…who knows…I might consider it.

Sherlock and I agreed earlier that I should change over to the…atomic bomb, i.e. take biocurcumax the way she is: once a day, all in one gulp. Forget about tickling my myeloma cells with a half dose twice a day. My gut feeling right now is that I want to blast the blasted myeloma cells with the entire arsenal, i.e. the full dose. At this point, I should mention that I am a pacifist in real life, but when it comes to myeloma cells, well, I feel like crawling down my bone marrow with a bow and curcumin-containing arrow and hunt the malignant cells down one by one.

I am going to look over my tests this weekend, and Sherlock and I will come up with a plan for March. Tomorrow Stefano is driving to southern Italy with his parents and brother to make sausages and whatnot out of a poor dead pig (I tried to save the pig’s life, but was outnumbered…this is a long-standing family tradition), so I will be “alone” in Florence with the four kitties. Plenty of time to study this issue. And go play cards with my girlfriends. Life is good.

PERSONAL SUCCESS STORIES

January 30, 2008 / / 4 Comments

A couple of days ago a blog reader privately suggested that I create a permanent page listing all the personal stories that have been published on my blog and the ones that may get posted (in the comment section only) in the future. This will ensure that they won’t get "lost." It’s true, I have more than 250 posts now, so yes, blog readers’ stories will eventually be impossible to find again, even for me! So this is a brilliant idea, thank you!

Below I list only the three stories published in the comment section of my January 27 post, but there are a few "older" stories listed on the permanent page (right-hand side of my homepage). Yesterday, in fact, I took off some time to go through some of the older post comments searching for personal stories (I will post only the ones that have been published on my blog; I will NOT publish any personal exchanges, of course, no worries), but I may have missed someone, so please remind me if you don’t see your story posted here. I have taken the liberty of editing out the parts that I thought less important, but feel free to scold me if I took out too much.

And by the way, I will be happy to post any stories concerning supplement-taking and dietary changes, so please don’t hesitate to send me the details. Now and in the future. And you can also send me updates as your story progresses. They don’t have to be success stories, necessarily, of course.

The following is not paraphrased, but is in your (blog readers) own words.

January 25 2008 post. Sherlock’s story: "I’ll just say how I took my curcumin capsules (8 gr./d). I took them all together (I follow a personal theory of the ‘atomic bomb’), late in the afternoon or late at night. I’ve not been very regular in the way I took them because I work out of town and sometimes is really difficolt for me to get hot milk and melt there 16 capsules of curcumin. So I used different systems, according to the situation:

– capsules melted into hot milk
– capsules taken drinking hot milk
– capsules taken drinking cold milk (not so often)
– capsules taken with just water

sometimes my stomach was empty, somethimes was full.
When I melted the capsules into hot milk I added either some olive oil, or some butter or some chocolate. Most of the time I did not add anything. My protocol also included 1.5 gr of quercetin and 1 gr. of fish oil every day. That’s all. I’m very happy that curcumin worked even if I changed the method of assumption according to my daily schedule. I think the most important thing has been to take all the 8 gr. together. My body knew that once a day a big dose of curcumin was going to cause apoptosis where it was needed."

JHope (she has been taking curcumin for more than two years, as I recall): "I have been taken curcumin – approximately 10 grams/day in podwer form (with bioperine) dissolved in hot milk. I also add fish oil (lemon flavor). I have been doing this for 2 years. My IgA marker has improved to the point that last test in December it was only 63 points above normal. This week I went to see a multiple myeloma specialist and shared with him what I was doing and he said to continue taking it that he has another patient that is doing the same and his numbers have improved tremendously. He also suggested to drink green tea.

Earl: "I have comments that could be helpful to others. My wife passed away 10 years ago due to MM. Five years ago I got a “pre-cancerous” prostate called high grade PIN. The doctor said there is nothing you can do except watch it……..I said, ” I think not.” I came up with a plan after checkng the internet extensively. I was able to REVERSE the pre-cancerous cells; as of August 13, 2008, they became non-existent. It was the last of three biopsies. Big picture: I went to an ALL organic diet; got a vita mix and drank approx 48 ounces a day of vegetables (Kale, broccli, red cabbage,parsley,carrots, and apples)…it tasted awful but I didn’t care. Also took “ground” flaxseed, cod liver oil, Aloe Vera, Vit c, N acyetal cysteine (NAC), Saw Polmento, Zinc, and selenium. Walked 45 minutes every day, lost 25 lbs and never regained the weight, stopped smoking and drinking. I stopped eating red meat and went to free range chicken and wild catch fish. BIG PICTURE: I placed all good things in my body and kept out the bad. The doctor reluctantly said I have changed the cell structure back to normal again. I have added curcumin the last 2 months: result, my triglycerides went down to 71 and my CRP, C-reactive protein is .2 The inflammation in my system is about 0…..a very good indicator of no cancer. If this article helps someone I will be happy. I too watched test results for 12 years and know the fear and excitement with bad and good results. I was VERY disciplined…..I realize that. But I made a choice to live and it worked. Sincerely Earl"

The dandelion phenomenon, part II

January 28, 2008 / / 3 Comments

Picking up from where I left off yesterday, the first type of cancer to be linked to stem cells was chronic myeloid leukaemia, or CML. The Johns Hopkins researchers proceed with a lengthy discussion on a drug called imatinib, which is used in CML, but without much success in the long-term. CML patients relapse if they discontinue imatinib (which, the researchers tell us, is currently being used more than interferon-alpha or IFN), or their cancer progresses even while they are on it. There appears to be no survival advantage in taking imatinib. The explanation, the researchers suggest, may lie in the CML stem cell resistance to this drug.

They use the dandelion analogy: “This pattern of activity is analogous to cutting a dandelion off at ground level. Although this will eliminate the visible portion of the weed, the unseen root also needs to be eliminated to prevent regrowth of the weed.”

Contrary to what happens with imatinib, CML patients’ response to the above-mentioned IFN is slow and gradual, “but can be durable.” So IFN would appear to act against the CML stem cells. Then we read “Thus, treatments that selectively attack cancer stem cells will not immediately eliminate the differentiated tumor cells. In this situation, cure (elimination of the cancer stem cells) in effect precedes the clinical demonstration of complete remission (clearance of the differentiated cancer cells) and could occur without actual disease shrinkage.”

This explains why these researchers took such a strong stance against the above-mentioned theory of complete remission. Complete remission may last months or years, but the cancer will return, eventually, unless the cancer stem cells are targeted. A treatment that targets cancer stem cells, however, won’t necessarily affect the circulating non-stem cancer cells. Hence, in this scenario, cure occurs before complete remission. This is contrary to everything I have read on the myeloma patient listservs (where a lot of the focus is on complete remission, or CR as we write it) and in the official myeloma literature. There are heaps of studies on the importance of complete remission in myeloma, in fact.

The researchers go on to discuss bortezomib (marketed as Velcade), a proteasome inhibitor, and lenalidomide (marketed as Revlimid, a derivative of thalidomide) commonly used in the conventional treatment of myeloma. These two drugs “can inhibit myeloma plasma cells but appear to have little activity against myeloma stem cells in vitro,” which means that they are pruning only the visible part of the dandelion, whereas rituximab, a monoclonal antibody, targets myeloma stem cells, i.e., the dandelion’s roots, according to the Johns Hopkins team.

The danger, the researchers point out, is that “As with IFN in CML and rituximab in myeloma, therapy directed against cancer stem cells might be prematurely abandoned if clinical activity is judged solely by criteria that reflect the effects of treatment on the bulk of the cancer.” And in fact, they add,“Not surprisingly, rituximab was found to have limited activity against myeloma in a short-term clinical trial. Rituximab’s activity against myeloma stem cells probably could not have manifested as immediate clinical responses in this trial because of the persistence of the long-lived, but terminally differentiated, myeloma plasma cells.” There you go.

So when we target stem cells, we must be patient. Unfortunately, nowadays, patience is no longer a virtue. We want to see immediate results. Overnight.

The researchers suggest setting up a clinical trial using bortezomib against the bulk of the cancer cells and then rituximab against the myeloma stem cells. Almost two years and a half have passed since this study was published. I went to have a look at the clinical trials being conducted right now. There are 591 trials (!) testing rituximab. I narrowed my search to myeloma, and found that there are 18 trials using rituximab alone or in combination with other drugs, such as lenalidomide or melphalan. Only one study, at the Dana-Farber Cancer Institute, is being conducted with rituximab and bortezomib, but for patients with Waldenstrom’s macroglobulinemia.

Well, these are certainly interesting times. I am all in favour of the dandelion theory, and it is for that reason that I am monitoring the DMAPT clinical trial, which should be beginning soon. (I admit to being more interested in substances such as DMAPT than in rituximab.)

The trees that are slow to grow bear the best fruit. (Molière)

The dandelion phenomenon

January 27, 2008 / / Leave a comment

This post turned out to be way too long, so I decided, as I have done with a few other posts that got out of hand (!), to divide it into two parts. I will post the second, longer "chapter" tomorrow.

Yesterday I read, and was spellbound by, a study on stem cells conducted by Dr. Matsui et al, and published in “Blood” in September 2005. The full study is available online: http://tinyurl.com/2539p7 An extraordinary study that makes some interesting points concerning “current methodologies used to develop new cancer therapies.” I thought I would highlight some of them (conventional methodologies only are discussed, by the way), even though you can go read the full text for yourselves: it’s easy to read, unlike most scientific texts. A real pleasure!

The abstract starts out with the following statement: “Although most cancer patients respond to therapy, few are cured. Moreover, objective clinical responses to treatment often do not even translate into substantial improvements in overall survival.” As various studies have shown, they write, the response of myeloma patients to chemotherapy does not lengthen their survival. An explanation for this could lie in the cancerous stem cells: “a rare population of cells that exclusively maintain the ability to self-renew and sustain the tumor.”

Now let’s have a look at the full study. The researchers immediately take a strong stance on the issue of "clinical response": “More than 30 new anti-cancer drugs have been approved over the past two decades. Approval required all of these drugs to show a clinical benefit, which can be documented by objective measurements of tumor response, improvements in quality of life as assessed by questionnaires, or a delay in the time to recurrence. However, these benefits have led to only modest increments in survival for the majority of cancer patients. Emerging laboratory and clinical data are beginning to point out potential flaws in the current methodologies used to develop new cancer therapies.”

What happens today is that when patients respond to a drug in a clinical trial, that drug is developed and made available as quickly as possible, with the idea that it will have an impact on the patients’ survival. If clinical trial designers, however, had to take into account “recurrence or an improvement in overall survival,” they would have to deal with very complex issues, such as large numbers of patients and allowing enough time, probably a lot of time, for follow-up.

The researchers do add that “objective responses” to chemotherapy may decrease side effects and improve quality of life. The issue at hand, though, is survival, for which “there is surprisingly little evidence.” As far as multiple myeloma is concerned, for instance, “neither the magnitude nor the kinetics of clinical response has an impact on survival.”

The researchers strongly criticize the concept of complete remission: “In actuality, the major rationale for the use of objective clinical response as a surrogate for biologic activity is the premise that a complete remission must precede cure.” They declare instead that “a complete remission by standard criteria may be neither a prerequisite nor a requirement for the actual generation of a cure.” This will become clearer as we proceed through the text.

Before signing off, I would like to urge everyone to read Earl’s story, in case you haven’t already done so (Beth posted his story on her blog, and I posted about her…post in early January). See his comment on my January 25^th post. Have a great Sunday!

A look at the full “Science” twin study

January 24, 2008 / / 8 Comments

I read and reread (and rereread…) this full study (grazie, Sherlock!) that I reported about in my January 19 post. Definitely one of the the most difficult texts I have ever read, and I have read some labyrinthine stuff, believe me! Anyway, a few things are clear (more or less…?), so I thought I would post about them today, hoping not to make any huge mistakes…

An important finding is that the pre-leukaemic stem cell population derived from the abnormal merging or, to use a more appropriate technical term, the “chromosomal translocation,” of two genes during pregnancy. From their union sprang a fusion gene called “TEL-AML1,” a clone that forms in one twin inside the womb that “may spread to the other twin via their shared placenta.” It’s a genetic “mistake” that can lead to the development of leukaemia. Or not, as in the case of these British twins.

In fact, the study tells us that “Additional mutations are required for progression to leukaemia,” which means that one twin may develop leukaemia while the other remains healthy, in spite of carrying the “ancestral preleukemic clone.” The researchers found that Isabella (the healthy twin)’s peripheral blood contained a “rare population” of these mononuclear cells, which has remained stable. This would prove that one mutation alone does not trigger full-blown leukaemia.

The “cancer-propagating population," or "rogue stem cell population," (which I like better) was present in both twins, but there were differences between the two. In the leukaemic twin, there was “a clonal and more differentiated descendant of the CD34+CD38–/lowCD19+ population in the healthy twin. Consistent with this, the majority of CD34+CD38–/lowCD19+ cells in the leukemic twin express common ALL antigen, CD10; those in the healthy twin do not.”

I know, I know…but this long string of letters and numbers, CD34+CD38–/lowCD19+, simply indicates the cancerous stem cell population. So the healthy twin’s cells present less differentiation, in sum. And her blood does not carry the acute lymphoblastic leukaemia (ALL) antigen, called CD10. Am I the only one who finds this fascinating? If not, and if you are getting a headache, just skip to the bottom of my post, where I wrote a summary of sorts.

The researchers then injected these pre-leukaemic cells into NOD/SCID mice. NOD (I looked it up out of curiosity) are “non-obese diabetic” mice. SCID are “severe combined immunodeficient” mice. SCID mice are frequently used in research dealing with the immune system in part because they lack the capacity to make T or B lymphocytes (so they cannot fight infections). I must say, I have a hard time reading all these details. When I was a kid, I would burst into tears whenever I heard about suffering, hurt or dead animals of any size. In many ways, I am still that kid. I haven’t been able to watch the "March of the Penguins," for instance. Or that wonderful movie about migrating birds…(when the hunters began shooting at those beautiful birds…well, you can imagine the rest!) Or even…"Bambi." I may be the only adult in the western world who hasn’t seen Bambi. But that is neither here nor there. It’s just that these feelings of empathy curtail my current plans to become a molecular scientist in my next life. I think I’d gather up all the mice in the lab and take them home…

But let’s get back to the study. What the team of researchers found was this: “Collectively, our data support the notion that TEL-AML1 can, as a single mutation, generate abnormal cells that resemble the TEL-AML1– expressing CD34+CD38–/lowCD19+ cells observed in the healthy twin.” If I understood this correctly, this means that the researchers were able to reproduce the pre-leukaemic population in the NOD/SCID mice. The transplanted cells resembled those found in the healthy twin’s blood and “displayed B cell differentiation and self-renewal potential in vitro.” They also did not contain the CD10 antigen, like the healthy twin’s peripheral blood cells.

The team then transplanted the rogue stem cells from the “primary” (first bunch of) mice into a bunch of “secondary” NOD/SCID mice: "To investigate whether the TEL-AML1–generated CD34+CD38–/lowCD19+ population can initiate and maintain a ‘preleukemic’ state in vivo, we prospectively isolated these cells from engrafted primary mice and injected them into the tibiae of secondary NOD/SCID recipients.”

These cells not only engrafted but, to the team’s surprise, also “gave rise to more mature B cells (CD38+CD19+), as well as reconstituting a CD34+CD38–/lowCD19+ population.” This means that the stem cell population, or “TEL-AML1–generated CD34+CD38–/lowCD19+ population has significant self-renewal potential.” What does all this mean? It indicates that this CD34+CD38–/lowCD19+ cell is able to reproduce itself, and it “may itself function as a preleukemic stem cell. This proposal is supported by our xenograft modeling studies, which further suggest that TEL-AML1 may be sufficient to generate this population of preleukemic stem cells.” Ok, TEM-AML1 is definitely the bad guy in this scenario.

The team also suggests that there is a hierarchical structure not just in full-blown leukaemia but also in pre-leukaemic cells. I am not sure why this finding is important, but apparently it is. If anybody knows the answer (I don’t have time to look into this matter now), please let me know.

Anyway, the study of the stem cell population, the researchers add, is crucial in order to understand “the function of the first-hit mutation and how it predisposes to leukaemic transformation.” Okay.

The study ends as follows: “The observation that children in lengthy remission can relapse late with a novel leukemic clone, but which nonetheless appears to derive from the identical preleukemic clone that initiated the disease at presentation, suggests that the preleukemic stem cell compartment may persist even when the cells propagating the overt leukemia have been effectively eradicated.” So the model created by these researchers may provide an explanation as to why pre-leukaemic stem cells can resist chemotherapy treatments. When that (resistance) happens, sooner or later the cancer will return.

There have been other studies on twins and ALL. I just wanted to highlight this one, published in "Leukemia" in 2003: http://tinyurl.com/ypom65 In this case, both twins (two years old) developed ALL. Here, too, the researchers suggested that these pre-leukaemic cells formed in the womb and spread from one twin to the other. And the researchers state that "It is likely that one or more additional postnatal genetic events was required for overt leukemogenesis." Aha, the "two mutations needed" theory that we discussed previously. Okay, that’s it for today. I still have my classes to prepare for tomorrow! Agh!

Summary of the 2008 study, as I understand it:

Acute lymphoblastic leukaemia (ALL) is the most common form of childhood leukaemia.
Researchers identified a “rare population” of CD34+CD38(-/low)CD19+ cells isolated from the TEM-AML1-positive twins.
The leukaemia-causing potential of this small population was confirmed when the researchers were able to transplant the cells of the leukaemic twin into a group of NOD/SCID mice. Successfully. And a second transplantation, from the first to a second group of mice, was also successful. The rogue stem cells survived and proliferated in the second group, too.
This indicates that these cells are self-renewing leukaemic stem cells.
The healthy twin only had one genetic defect, whereas the leukaemic twin also carried a second genetic mutation (the loss of the "uninvolved" normal TEL allele or gene, for the science brains among us).
The second mutation may have been triggered by an infection, which may have led to the development of leukaemia in one of the twins. No second mutation = no leukaemia, then, it would seem.

NF-kB: Dr. Jekyll or Mr. Hyde?

January 22, 2008 / / 6 Comments

A blog reader and I recently had an interesting exchange about this transcription factor, which is so important in myeloma…in a negative sense, unfortunately. Our discussion gave me the incentive to read more about it. My good friend Sherlock (grazie!) sent me a study published in January (2008) in “Experimental Biology and Medicine,” titled “Nuclear Factor-kB Activation: From Bench to Bedside,” and co-authored by Prof. B. Aggarwal (abstract: http://tinyurl.com/2m6j2g).

This transcription factor, discovered in 1986, was called NF-kB “because it was found in the nucleus bound to an enhancer element of the immunoglobulin kappa light chain gene in B cells.” Okay, wrap your brain around that! But seriously, if you reread the quote slowly, it begins to make sense: it’s a thingie (protein complex or transcription factor) sticking to the “kappa” gene inside a B cell’s nucleus.

Under normal circumstances, our immune system needs NF-kB to fight off diseases and infections. And until it is needed, this transcription factor follows my cats’ example and takes a lot of very long naps. I don’t want to go into its mechanisms of action (complicated stuff!), at least not today. Let it suffice that, once it has accomplished its task, it settles back down for another nap.

The study informs us that NF-kB is present in every type of cell, not just B cells as was first thought. Researchers have in fact discovered that it is located in the cytoplasm (the watery environment surrounding the cell nucleus) of all types of animal (from the fruit fly to us) cells. Another important finding is that it moves, or translocates, to the cell nucleus only when activated. Otherwise, it stays in, or (once it has finished its task) goes back to, the cytoplasm.

Things change with cancer. That’s when NF-kB turns into Mr. Hyde: it goes bonkers for a variety of reasons and ends up being active ALL the time, or constitutively active. And when this happens, NF-kB remains inside the cell nucleus, that is, it doesn’t return to the cytoplasm. No more naptime!

Skipping the technical parts about heterodimers, polyubiquitination and nuclear localization sequences (!), let me get to what we are really interested in: how does this transcription factor get activated in cancer cells? The study provides an answer: “NF-kB is activated by many divergent stimuli, including proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), epidermal growth factor (EGF), T- and B-cell mitogens, bacteria and lipopolysaccharides (LPS), viruses, viral proteins, double-stranded RNA, and physical and chemical stresses.” Radiation and chemotherapy also activate NF-kB. Speaking of which, the study tells us also that "Cells that express constitutively activated NF-kB are resistant to various chemotherapeutic agents and radiation treatment.” Vicious circle?

Another key sentence: “In tumor cells, different types of molecular alterations may result in impaired regulation of NF-kB activation. In such cases, NF-kB loses its transient nature of activation and becomes constitutively activated. This leads to deregulated expression of NF-kB– controlled genes.” NF-kB, the study continues, plays a critical role in cancer cell survival, inflammation, growth and so on. It regulates genes that are implicated in cancer cell proliferation, including TNF-alpha, IL-6, to name just a couple that we know are essential growth factors in multiple myeloma. It also regulates some of the cell cycle-regulatory proteins such as cyclin D1, also involved in myeloma (see my page on Ursolic Acid or my December 4 2007 post for more info on this gene, which has recently been associated with disease activity and progression).

Activated NF-kB is also implicated in the control of anti-apoptotic genes, that is, genes that keep cancer cells healthy and alive, such as survivin and Bcl-2 (again, see my post on ursolic acid). Furthermore, it regulates matrix metalloproteinases, or MMPs, which are proteases (protein-dissolving enzymes) that, among other things, promote cancer cell growth and angiogenesis. Okay, so there is no question that constitutively active NF-kB is not a good thing.

That’s enough for today, but I would like to end with a question: if we systemically inhibit NF-kB in order to stop our cancer from progressing, doesn’t that leave us more susceptible to infections? (More on this topic SOON!)

Unlocking the secrets of leukaemia…

January 19, 2008 / / 10 Comments

A myeloma list member (thank you!) posted the link to a January 17 BBC story (see: http://tinyurl.com/2mol2c) about four-year-old identical twin girls were born with leukaemic stem cells (STEM CELLS!) in their bone marrow.These cells contained “a mutated gene, which forms when the DNA is broken and rejoined at another point. The pre-leukaemic cells are transferred from one twin to the other in the womb through their shared blood supply. But it takes another genetic mutation in early childhood for the cells to cause disease. This second mutation, which may be caused by infection, occurred in Olivia but not Isabella.” In fact, only Olivia developed full-blown leukaemia (acute lymphoblastic leukaemia or ALL). UK researchers examined the twins’ blood, and their findings were published in the January 18 issue of "Science." The abstract can be read here: http://tinyurl.com/285qjn.

“About 1% of the population is thought to be born with pre-leukaemia cells. Of these, 1% receive the second "hit" that leads to cancer.” Even a simple cold, from other articles that I read online, is apparently able to trigger this second mutation.

Well, this is all very interesting. I remember that, when I was eight years old, my family doctor here in Italy was convinced that I had leukaemia. Unfortunately, my blood tests from that period are probably buried in a box in my parents’ garage in the U.S., but if I am able to locate them some day, they might yield some interesting information that could be relevant to my having myeloma (inactive) today. Could I possibly have had a “second hit” (later in life) that led me to develop this cancer? Well, this is just a random thought on a lazy Saturday evening. Nothing more. And indeed, now that I have written it out, it appears to be unlikely.

But the next time I visit my parents, I will comb through their garage, just in case.

Margaret's Corner

Month: January 2008