Another Celiac Disease Case Study

December 19, 2007 / / 6 Comments

Just a quick post today. These days I have heaps of things to do that are keeping me away from my computer and my research. Errands, work, cookie baking and whatnot. ‘Tis the Xmas season! Speaking of work, one of my students this morning wanted to say “I’m really sorry,” but what came out of her funny mouth was “Sorry davvero” (davvero means “really” in Italian). Yes, this was another merry teaching day. Oh dear, I just noticed that parts of my keyboard have turned yellow. Will I ever get the curcumin stains out? Hmmm.

Anyway, back to serious stuff. A friend (thank you!) sent me a case study published in 1980 and titled “Multiple myeloma and adult celiac disease.” It discusses the case of a 75-year-old woman with multiple myeloma (a bone marrow biopsy or BMB revealed 80% malignancy), a resident of Wisconsin, who “was admitted to the hospital because of diarrhea and abdominal pain.” She had had this kind of trouble for “25 years prior to admission.” So had a few close relatives. Her intestinal woes vanished after she began a gluten-free diet.

Keeping in mind that this study was written 27 years ago (!), let’s read the following: “The appearance of malignity in patients with celiac disease has been well described and several theories have been offered in explanation. An abnormal immune surveillance allowing for the development of a malignant clone of cells is most popular. Proponents of this theory cite the various studies demonstrating a defect in the immune apparatus, such as a reduction in the number of ‘T’ cells or immunoglobulins, or demonstrating a defect in immune function, such as impaired response to mitogens or reduced cytotoxicity. Other explanations include inherent genetic predisposition (celiac patients with malignancy have a higher frequency of having the histocompatibility antigens HLA-A1, HLA-B8, and HLA-B12), and the accumulation of dietary carcinogens because of the lack of detoxifying enzymes and appropriate cell turnover in the small bowel mucosa.” Hmmm. Detoxifying enzymes, eh? I must look into this when I have more time (hah!).

Further on, “Multiple myeloma, a malignant conversion of an immune functioning cell, had not been reported in association with celiac disease. It is tempting to speculate that chronic antigenic stimulation in a patient with abnormal immune response resulted in the plasma cell dycrasia. In patients with multiple myeloma who have persistent, unexplained diarrhea or steatorrhea, endoscopy and biopsy are indicated to rule out amyloid or celiac disease.”

Plasma cell dyscrasia, by the way, is a group of diseases characterized by the proliferation of a single clone of plasma cells. This clone produces a huge amount of a single antibody, or monoclonal antibody, known as M-protein. Multiple myeloma is part of this group and so are other plasma cell malignancies, such as Waldenstrom’s macroglobulinemia. And MGUS. I think it’s always good to review this stuff (sometimes I forget specifics, too!).

I don’t know if I have gluten intolerance. I certainly don’t have any of the harsh symptoms that I have seen described here (and there). But I want to take the antigliadin antibody test just to rule it out. Like Web Admin, I had a terrible diet for years, especially in college and grad school, when I couldn’t be bothered with cooking. I ate a lot of pasta and chemical-ridden sweets. Tons of gluten, in other words. At any rate, if it turns out that I have the slightest intolerance to gluten, I don’t think it would hurt for me to send it into exile forever. Even if my myeloma markers don’t decrease. Okay, I have more errands to run, so off I go! Ciao a tutti!

Myeloma and Diet: A Possible Connection

December 17, 2007 / / 9 Comments

I spent most of this past weekend baking butter-ridden, U.S.-style Xmas cookies and (of course!) tasting them since every year I try new recipes that have to pass my own personal and very strict “quality control” tests. Most of these cookies are full of stuff that’s no good at all for us (oh yes even white sugar and flour), with the possible exception of my oatmeal spice ones, which contain turmeric as well as other spices. So of course today I am posting about a study that makes a possible connection between what we eat and the risk of developing myeloma. Cookies don’t seem to be on the list of foods that prevent myeloma (although I may work on changing that). Hmmm, I wonder why…

The full study, published in the December 2007 issue of "Cancer Causes Control," is available online, see: http://tinyurl.com/ypswov). It was conducted in Connecticut on 179 women between the ages of 21 and 84, diagnosed with myeloma between 1996 and 2000. Since you can read it on your own, I won’t go into too much detail. I would like, however, to highlight a few of the most significant points:

“Only a handful of studies have evaluated the association between diet and multiple myeloma, and results have been inconclusive.” Previous studies, of course.
“Intakes of protein, fat, and dietary fiber were not associated with multiple myeloma risk.”
“Intake of vitamin A was associated with a statistically significantly decreased risk of multiple myeloma.”
“There were no clear associations between consumption of various fruits and multiple myeloma risk.”
“There was a suggestion of an elevated risk among individuals within the highest quartile of hard candy, jam, jelly, honey, and syrup […] consumption.” HONEY? Oh, bother!
“alcohol intake was inversely associated with multiple myeloma.” Coffee and tea made no difference.
The study gives us another reason to take omega-3, since these “essential fatty acids found in fish, have been shown to limit mouse myeloma cell growth in an experimental study.” Interestingly, omega-3 was a crucial supplement in the Washington Post story that I referred to in yesterday’s post. The cancer world appears to be a small world after all…

The study found that some dairy foods were associated with risk of developing myeloma: ice cream (drat!), custards and cream soups. Vice versa, higher intakes of fish, tomatoes, fruit, vegetables and alcohol were associated with a lower risk.

And read this: “In laboratory studies, vitamin D has been shown to inhibit growth of myeloma cells by inducing cell cycle arrest, down-regulating the anti-apoptotic Bcl-2 protein, and increasing the activity to caspase 3 protease, a regulator of apoptosis…” Okay, I admit, I have been collecting heaps of material on vitamin D, and I also have begun taking vitamin D3 once a week (thanks to my vitamin-D-obsessed-with-good-reason friend Sherlock), but I haven’t gotten around to dealing with this topic mainly because it’s so incredibly HUGE. I will figure out something over the holidays.

The study’s finding about tomatoes is interesting. One usually associates lycopene with prostate cancer prevention, but here it is suggested as being important in the prevention of myeloma, too. Oh, and the business about alcohol intake doesn’t mean we should all become heavy drinkers. It simply means, according to the study, that the flavonoids in beer and the resveratrol in wine may have a preventive effect. These researchers have the humility (I like that!) to point out that their sample size was very small and specific, that they had a low response rate and so on. More and better research is needed, clearly. Nonetheless, it was an interesting read.

Final point: I wonder if I have enough time before Xmas to come up with a luscious turmeric tomato broccoli codfish cookie? Hmmm.

Myeloma: An Acute Form Of Celiac Disease?

December 14, 2007 / / 13 Comments

A topic that has been discussed recently on a couple of websites, that is, Cancer Compass (http://tinyurl.com/2daxza) and Beating Myeloma, is the celiac disease-myeloma connection. There are a ton of studies on celiac disease, also known as gluten intolerance. According to this one (abstract: http://tinyurl.com/2hk8jj), it is: “an autoimmune inflammatory disease of the small intestine that is precipitated by the ingestion of gluten, a component of wheat protein, in genetically susceptible persons. Exclusion of dietary gluten results in healing of the mucosa, resolution of the malabsorptive state, and reversal of most, if not all, effects of celiac disease. Recent studies in the United States suggest that the prevalence of celiac disease is approximately one case per 250 persons.” Now, I grew up in Italy on a pasta diet. I LOVE pasta and cannot imagine my life without it. But this topic concerned me enough to buy some gluten-free pasta and think about going on a gluten-free diet at some point early next year. Let’s have a look at a few of these studies.

A study (abstract: http://tinyurl.com/2hfhgz) published in “Leukemia Research” in December of 2006 points out that “it is well known that in sera of some patients with intolerance to gluten, with celiac disease, the IgA or IgG immunoreactivity to gliadin, and elevated levels of IL-6, could be present too.” Gliadin is a glycoprotein (a carbohydrate plus a protein) found in wheat, oats, rye, barley and other cereals.

Now, this is very interesting. Let’s see: 1. Gluten intolerance is associated with high levels of IL-6. But people with celiac disease also have high levels of IL-1beta, which strongly induces IL-6. Not good. 2. The immunoglobulins IgA and IgG are involved in the immune system reaction to gliadin. What a coincidence, huh? Hmmm.

This study is the first to report “that antibodies from some M-component could be directed to gliadin antigens.” Even though more research is needed, multiple myeloma could possibly be a “more severe form of gluten intolerance than celiac disease,” connected to our immune system’s reaction to gliaden antigens. In other words, those who have this particular food intolerance could possibly and eventually develop myeloma. Did I understand this correctly??? I am almost at a loss for words.

Another excerpt: “As IgA or IgG antigliadin immunoreactivity found in sera of patients with celiac disease is diminished in patients on gluten-free diet (GFD) and by some antibiotics, it could be of importance to consider whether the same approach in patients with MM (and with antigliadin immunoreactivity), applied at the end of conventional therapy would stop myeloma progression.” How about that? Go on a gluten-free diet, as some myeloma and MGUS folks in my acquaintance already have, and see if that is enough to stop myeloma from progressing. Who knows?

Another 2006 study, published in “Aging Clinical and Experimental Research (full study: http://tinyurl.com/ythyfm), tells us that “Although lymphoproliferative disorders and intestinal tumors are the most commonly seen malignancies, many other malignancies including multiple myeloma may develop.” The study examines the specific case of an elderly patient who was eventually diagnosed with celiac disease, after 15 years of diarrhea and other symptoms. “In our case, failure of diagnosis despite 15 years of symptoms played an important role in the development of malabsorption-related complications such as anemia, electrolyte imbalance and osteoporosis, as well as multiple myeloma.” I noticed a rather curious thing: the abstract tells us that the patient had plasma cell dyscrasia but not myeloma; then the full study states that the patient was diagnosed with early-stage myeloma. Odd. Oh well. Point is, though: this study affirms that myeloma may develop in patients with celiac disease.

A 1990 German study (http://tinyurl.com/yrlfa3) examined the fate of 52 people diagnosed with celiac disease: 15% of them developed cancer, including one case of myeloma. A 2004 Irish study (http://tinyurl.com/28gkm9), titled “Celiac Disease and Malignancy,” looked at 77 patients with celiac disease. One had myeloma. Interesting statistics, if nothing else. Could there be a gluten intolerance connection for some of us? Isn’t it worth at least getting tested?

Concluding remarks: I recall having an array of allergy tests done several years ago, and I distinctly remember that I was not allergic to wheat (etc.). But things change, so I am going to ask my haematologist what she thinks about it. After all, a simple blood test can determine if one has the antigliadin antibodies. Easy peasy!

TEST RESULTS IP IP URRA’!

December 13, 2007 / / 4 Comments

I wrote this post on Monday, December 10th, after receiving my November test results (here in Italy, we patients receive our test results, not our doctors, which I personally think is great). Since I received more than a dozen comments (that were gobbled up by voracious Mr. Server during the updating process), I decided to create one BIG comment instead of several individual comments. As things stand, it really looks as though I wrote all those comments myself, but I didn’t, I didn’t, I promise! Here is the original post:

Spettacolare!, as we say in Italian! And here I was, dreading the arrival of my test results since I took them during a period of (a bit of) stress, I had just begun my new job etc. Well, HURRAY definitely replaces DREAD! But let me proceed by degrees.

I will compare these tests, taken on November 19th, to my not-so-good-but-still-semi-okay September tests. My IgG has dropped from 34.3 (September) to 27.8 g/L (now). The normal range is 7-16 g/L. I have always been terrible at math, but that’s almost a 20% drop, no?

My IgA and IgM are as stable as rocks, haven’t moved a bit, but that is ok with me, even though both values are very VERY low. The important thing is that they didn’t go any lower!

My blood viscosity has dropped from 55 to 48 mm/hour, which is good. Keep in mind that this value has gone as high as 95! My white cells have climbed a bit, from 4.63 to 4.98; my red cells dropped just a teeny tiny fraction. My haemoglobin is stable in the region of 13, and my hematocrit has increased a bit, from 38.1 to 39.5 (normal range: 36.0-46.0). Creatinine is stable at 0.7, within the normal range; calcium is slightly up but still way within the normal range; albumin is still within the normal range (yippee). Bence Jones is NEGATIVE (yeah, yeah, yeah!). Beta-2 Microglobulin has gone down slightly, from 1.8 mg/L to 1.6 (normal range: 1.2-2.5 mg/L). Also good.

Not much really stands out in a negative sense. My serum iron, however, has dropped from 109 to 62 micrograms/dL (normal range 60-140 mcg/dL), so I will have to do something about that. Yikes. I see a few steaks in my near future. But my ferritin, which was 7 ng/mL in June, then 8 in September, is now 10 ng/mL (normal range begins at 15). Still low, but going in the right direction, at least. Oh, my total cholesterol went up somewhat (but so did my HDL, the good cholesterol, so that is good), but I expected that to happen, since for more than a month and a half I tested a concoction based on a dab of butter and either double cream or whole milk, so I suppose even curcumin couldn’t battle against THAT! Have I forgotten anything? Oh, my m-spike is also stable, in the 2 region.

In sum, all is well! SUPER DUPER WELL! Little dance of joy today! 🙂

Stress Involved In Myeloma Progression: Very Evil Growth Factor

December 13, 2007 / / 1 Comment

Today I will be putting back a couple of posts, including this one, which I posted on December 7, 2007. The original posts were gobbled up by the server, apparently, comments included. I will put the comments back as best I can. Sorry if they look funny! Not funny haha, funny weird. 😉

Other myeloma bloggers have posted about a recent study (abstract: http://tinyurl.com/2w4ndb) showing the link between myeloma and stress. My friend Sherlock sent me the full study, so I will try to provide some additional information. Conducted by a team of researchers at the Ohio State University Medical Center, this study was published in November 2007 in “Brain, Behavior and Immunity,” which by the way looks like a very interesting publication. I must keep my eye on it.

The study is titled “VEGF is differentially regulated in multiple myeloma-derived cell lines by norepinephrine.” A couple of notes before proceeding. Noradrenaline, also known as norepinephrine (NE), is a hormone and neurotransmitter involved in alertness and concentration, among other things. It is involved in heart rate, blood pressure and blood sugar level increases. VEGF stands for “vascular endothelial growth factor,” and is an evil signalling protein that is linked to tumour progression, feeding cancer cells, etc. Read this excerpt from an IMF article written in 2001 (http://tinyurl.com/2yh49k): “Dr. Kenneth Anderson of the Dana-Farber Cancer Center mentioned that VEGF might not only be important for the formation of new blood vessels in MM but also has the potential to stimulate directly the proliferation and migration of myeloma cells. His group demonstrated that production of VEGF by myeloma cells can be stimulated by activation of the CD40 molecule on the surface of the tumor cells.” CD40, we meet again!…remember my CD40 post? I am not done yet with natural ways we can use to inhibit CD40, I just need to find the time to read the studies that Sherlock sent to me.

But let’s get back to VEGF. The Ohio stress study tells us that “VEGF is a crucial cytokine that directs and promotes tumorogenesis and potentiation in the marrow. VEGF levels correlate with overall prognosis and associated bone destruction, which contributes substantially to clinical morbidity.” I told you VEGF was evil! In fact, I suggest that from now on it be known, perhaps more appropriately!, as “Very Evil Growth Factor.”

The introduction begins: “There is evidence that psychological factors can affect the incidence and progression of some cancers.” And, in fact, there is definitely a connection between our IL-6 levels and chronic stress, which is actually a topic on my infinitely long to-be-researched list. That is one reason why I was most interested in the finding, reported in the Ohio study, that NE has been found to stimulate IL-6 and IL-8 in human melanoma cells. But these two cytokines are also actively involved in myeloma. We know all about evil IL-6, but IL-8 has also been connected to progression in myeloma. No comment necessary, methinks.

Discussing a previous study, the Ohio researchers report that stress can inhibit T cells from responding “to tumor-associated antigens on tumor cells of immunogenic tumors.” T cells, hmmm, that sounds familiar.. And the effects caused by stress may “may contribute to tumor progression independent of its effects on the immune system.” Well, we knew that stress is bad for us, but this goes a bit beyond “bad.”The researchers tested three myeloma cell lines in different stages of development. All three had “the potential to respond to NE,” but one in particular “exhibited the greatest NE-dependent response.” Interestingly, this cell line came from someone whose myeloma was aggressive but ”in the earliest (and comparatively longest) clinical phase—i.e., where disease is confined to the bone marrow.” This could mean that in early stages perhaps the blood supply to the malignant cells could be diminished simply by inhibiting NE, which would not kill the malignant cells, of course, but should theoretically slow down tumour growth and disease progression.

Toward the end of the study, we find the following: “Whether the stress-associated activation of the sympathetic nervous system results in the upregulation of NE levels in the bone marrow is unknown. However, observations described here suggest the potential for a stress-associated stimulation of proangiogenic properties of MM cells through the upregulation of NE levels.” The Ohio team adds that “the mechanism involved in the NE-dependent increase in VEGF release by MM cells is not known.”So let’s have more studies like these instead of inanities of the following sort (I glanced at this article this morning and could hardly believe my eyes): “new research suggests that the presence of other people may enhance our movie-watching experiences. Over the course of the film, movie-watchers influence one another and gradually synchronize their emotional responses” (http://tinyurl.com/299s5x). Ehhhh??? You’ve got to be kidding. Isn’t it common knowledge that if you go see a fantastic movie with someone you don’t like, most likely you will hate it, but if you go to see the same movie on your own or with a good friend, you will probably love it, blablabla? Do we really need actual STUDIES to look into this sort of twaddle? Come on!

I would like to finish by saying that I hope to have time at some point to look at the other NE-cancer studies. The one I read today deals specifically with myeloma, but the other NE studies examine other types of cancer. And then there is the whole related issue of beta-blockers, which the Ohio team suggests might be beneficial for myeloma patients (but more info is needed, they add). Anyway, that topic too complicated to get into today. Interesting, though. Okay, have a fun laughing weekend, everyone!