Zalypsis

December 11, 2008 / / 4 Comments

It sounds like the name of a new videogame or a deadly disease, but Zalypsis is actually a newly-discovered (by a University of Salamanca research team) potent anti-myeloma substance, a new synthetic alkaloid related to various compounds isolated mainly from marine sponges. You can almost envision the excitement of these Spanish researchers when they declare that Zalypsis is the most active antimyeloma agent tested in our laboratory (see study abstract: http://tinyurl.com/59faqe). Further on, in the full study, they write that Zalypsis is at least 10 times more potent than any of the antimyeloma agents we have tested so far. 10 times…wow.

Okay, I will now launch into the full study, provided by Sherlock (grazie!) and pointed out to me by a blog reader (another grazie!).

Zalypsis was tested on nine different myeloma cell lines and bone marrow samples from myeloma patients. In every single case, including two cases of plasma cell leukaemia, it killed the cancerous cells. Apoptosis…

As for Zalypsis and healthy cells, I thought it would be good to copy the relevant paragraph: Upon analyzing the efficacy of a new agent a mandatory experiment is to investigate its toxicity in normal cells. These experiments are usually conducted on normal peripheral blood samples. We have developed an ex vivo technique that allows to simultaneously analyze the cell death induced by a particular agent both on the malignant cells and the residual BM cells. Now, for the first time using multiparametric flow cytometry, we have analyzed the action of Zalypsis on the cell subset that mainly corresponds to the normal stem cells (CD34+, CD38-, CD33-) and have seen that Zalypsis does not affect this cell population although is toxic for the more mature myeloid population. So, good news. Too bad that Zalypsis, from what I gather, is not effective against the myeloma stem cell population…

Another important discovery: Zalypsis inhibited IL-6 and eliminated the protection offered to myeloma cells in the bone marrow microenvironment, which confers protection to myeloma cells through their adhesion or through the production of several cytokines such as IL-6 […]. Precisely. Excellent.

Zalypsis was also found to work in synergy with and increase the efficacy of Dexamethasone, Melphalan, Doxorubicin, Bortezomib and Lenalidomide, which are all conventional drugs used to treat myeloma. In particular, it was effective when combined with Dex and Lenalidomide. It also increased tumour-killing p53 levels in most cell lines, more effectively and strongly than doxorubicin.

And remember our “friend,” Bcl-x? Well, Zalypsis also inhibited Bcl-x (but not Bcl-2; well, we can’t have everything…).

According to the researchers, Zalypsis has been found to have an acceptable toxicity profile. In this particular “Blood” study, they tested Zalypsis on three groups of mice (one control group and two groups receiving different Zalypsis doses) and found that no significant systemic toxicity was associated with Zalypsis treatment, and only a slight weight loss (around 10% of body weight as compared to the controls) was observed with the highest of the doses. Nevertheless, an important local toxicity was caused at the site of injection of Zalypsis with ulcerations and necrosis of the tail in some of the mice. Ok, we aren’t mice and don’t have tails, but should we be concerned?

The Phase I clinical trial (http://tinyurl.com/6yud2r) has ended. According to an October 2008 PharmaMar (the company marketing Zalypsis) press release (http://tinyurl.com/5tr5fu), […] the safety of Zalypsis in 37 patients with solid tumors or lymphoma was evaluated. The trial shows a good safety profile of the drug, which enables the continuation of its clinical development.

The press release informs us that Zalypsis was also tested in some childhood malignancies: The most significant results in in vitro tests were obtained in neuroblastoma and rhabdomyosarcoma cell lines. The evaluation of the compound in animal models also showed significant results, especially in the activity in rhabdomyosarcoma.

So, to sum up, Zalypsis was effective on myeloma cell lines that had become resistant to conventional chemo drugs. It worked synergistically with several anti-myeloma drugs, especially Lenalidomide and Dexamethasone. It also profoundly affected the growth of plasmacytomas in mice. The list goes on. Yes, it sounds like a very promising substance to me.

Study’s conclusion. The action of Zalypsis in MM therefore involves several interlaced pathways that move into an apoptotic response, likely initiated by direct DNA damage. These pathways may include p53-dependent and p53–independent routes that by acting on caspases and other apoptotic signalling pathways hamper MM cell proliferation and trigger apoptosis. The potent antimyeloma action of Zalypsis, together with the particular mechanism of action of this compound strongly supports the initiation of clinical studies in MM patients.

DMAPT: targeting leukemic stem cells

December 8, 2008 / / 7 Comments

Thanks to a Google Alert, yesterday I learned about a new article written by Craig T. Jordan, Ph.D., an Associate Professor at the James P. Wilmot Cancer Center, U of Rochester School of Medicine. Here is the link to the abstract: http://tinyurl.com/695g3g. As usual, I asked Sherlock (gracias!) to get the full study for me. Well, this was quite an interesting (and easy) read, which also gave me a few possible clues as to why the DMAPT clinical trial hasn’t yet begun in the UK. But let’s proceed by degrees, as usual.

Dr. Jordan brings up an issue that is no news to us: can the same results obtained in laboratory tests be obtained in patients as well? Eh.

He then mentions a series of small molecules, such as a proteasome inhibitor named MG-132, which target leukemic stem cells. But I would like to focus on what he writes about the substance that interests me perhaps above all others right now: parthenolide (PTL). As you may recall, I am currently testing a feverfew supplement that contains 3% PTL (the highest % I could find). I am taking the dosage recommended on the bottle, which is minimal, I know, especially since PTL is poorly bioavailable. I read that a group of cancer patients took as many as 4 grams of PTL/day in a 2004 Phase I dose escalation trial. I am presently taking less than one-fourth of that. But my motto is primum non nocere, and I am going to stick to it. I can always increase the dose, right?

So let’s see what Dr. Jordan has to say about PTL: Parthenolide, a naturally occurring molecule found in the medicinal plant feverfew, induces apoptosis in acute myeloid leukemia (AML) stem cells. Interestingly, he then mentions celastrol (see my Page on celastrol or “thunder of god”), which targets both “bulk” and stem AML cells. But his focus is on PTL.

And here we get to one of the most promising substances I have come across in my research, one that I dearly hope will quickly turn out to be effective and non toxic in Phase I trials: DMAPT, the PTL analogue. The acronym stands for dimethylamino-parthenolide. (I have a Page on PTL and DMAPT, by the way.)

Dr. Jordan tells us that, unlike PTL, DMAPT is readily water soluble and is 70% orally bioavailable. Pharmacologic studies in rodents and dogs have shown the drug to be tolerable well beyond the level at which in vitro activity is observed, without any known associated acute toxicity.

As we know from previous studies, in addition to inhibiting NF-kappa B, DMAPT targets ONLY cancerous stem cells, leaving healthy cells alone. And, When canines with severe acute leukemia were treated with 50 mg/kg daily DMAPT, the levels of CD34-positive cells were largely reduced.

A detailed description of an experiment conducted on animals (mice, mainly) follows. I won’t go into details, but the results were that leukemic stem cells were impaired, at least in the context of a large animal with a spontaneous leukemia.

This paragraph ends with words that sound like a Mozart symphony to my ears: Based on the preclinical findings, the drug is proceeding towards clinical trials. As my darling niece would comment, “Sweet!”

Dr. Jordan then provides a possible explanation for why it is taking so long to start the DMAPT clinical trials (this is my own interpretation, mind you, since the reason could merely be endless heaps of red tape): It is still unclear how to effectively assess whether leukemic stem cells are actually being targeted. Ah. Big problem, here.

He adds that A targeted agent could be used as part of a maintenance regimen to destroy the residual leukemic stem cells in patients in remission. However, he soon adds, there is no evidence that any of the agents currently available can target leukemia stem cells in a remission patient. Oh.

And then we get to a fascinating, thought-provoking excerpt: The biology of cells in minimal residual disease conditions appears to be very different from that of cells found in a de novo and heavy tumor-burden context. This difference can impact whether the drugs work or not. As clinical trials progress, the targeted agents may fail because of the physiology of the tumor cells, not because the drug is ineffective with all leukemic stem cells. Well then, I say, why not test DMAPT also on leukemic/myeloma patients who have never had any conventional treatments? (Not that I have anyone specific in mind… 😉 )

Reading on, we stumble upon what might be another reason for the DMAPT clinical trial delay: Cancers are heterogeneous, and this is exceptionally true of leukemic stem cells. From patient to patient, molecular markers for stem cells differ greatly. […] This heterogeneity makes determining the frequency of the leukemic stem cell in an individual patient extremely difficult.

Dr. Jordan defines leukemic stem cells as highly dynamic and highly unstable. So the question arises: how can they possibly be monitored? In comparison, it would seem that keeping individual tabs on millions of agitated grasshoppers in a field would be a much easier task…

As I see it, these seem to be the main problems facing clinical trial investigators: 1. how to identify the stem cells in each individual patient in the first place; 2. how to determine if these cells are being targeted by the specific treatment (DMAPT, e.g.).

And here follows something that perhaps for the first time I have seen spelled out in a study: During chemotherapeutic challenge, patients can experience a dramatic change in the phenotype of their leukemic stem cell. From my layperson’s point of view, it would appear that this “dramatic change” would also be a problem.

Furthermore, just because your total tumour burden decreases doesn’t necessarily mean that your stem cells have been affected. Another problem.

But there seems to be a way of getting around all of this. Dr. Jordan writes that Clinical trials must be temporal and patient-specific. Specimens must be gathered before, during, and after treatment. The phenotype of each patient’s leukemic stem cell population must be defined up front and verified by a functional assay to help quantitate it. In the course of treatment, the population must be continuously monitored […]. It sounds extremely painstaking and time-consuming, doesn’t it?

Dr. Jordan’s final considerations: Just as cancers are heterogeneous, so too are leukemic stem cells, and the ability to target and quantitate leukemic stem cells is complicated by this heterogeneity. As research expands our understanding of leukemic stem cell biology and physiology, investigators must incorporate that knowledge into their strategies for targeting and analyses for quantifying leukemic stem cells. They must also determine where agents that target leukemic stem cells will be of most use: as maintenance therapy that targets minimal residual disease in remission patients, or as treatment for relapsed or refractory patients.

To this, I would add: “…or as treatment for patients who have not yet had any chemotherapy.”

Tall women/heavy men at risk for myeloma

December 7, 2008 / / 6 Comments

A blog reader (thanks!) sent me the link (http://tinyurl.com/6cvgnv) to an interesting bit of statistical news. In an attempt to test the hypothesis that increasing obesity (=impaired immunity) might be a reason for the growing number of cases of multiple myeloma and non-Hodgkin’s lymphoma or NHL, the “European Prospective Investigation into Cancer and Nutrition” (EPIC) examined hundreds of cases all over Europe.* The results were published in “Haematologica” in October 2008.

The study concluded that height is a multiple myeloma (and NHL) risk factor for women just as weight is for men. Doesn’t that sound peculiar?

The full study is available at the above link, so I will quote only some of the relevant bits, as follows: Height was associated with overall non-Hodgkin’s lymphoma and multiple myeloma in women (RR 1.50, 95% CI 1.14–1.98) for highest versus lowest quartile; p-trend < 0.01) but not in men. Neither obesity (weight and body mass index) nor abdominal fat (waist-to-hip ratio, waist or hip circumference) measures were positively associated with overall non-Hodgkin’s lymphoma and multiple myeloma. This part then examines the risk associated with large B-cell lymphoma (heavier women are at risk) and follicular lymphoma (ditto for taller women).

MM has also been examined in a number of studies. In contrast to our finding of an elevated risk of MM among taller women, the Iowa women’s cohort study observed no association. Among men, the most prominent MM risk factors were weight, BMI and WC as categorized according to well-established definitions. (BMI=body mass index; WC=waist circumference.)

Factors that have been associated with multiple myeloma (MM) include high doses of ionizing radiation, and occupational exposure to products used in farming and petrochemical industries. Not my case, as far as I know.

In conclusion, the study found that height was a strong risk factorfor NHL and MM risk in women.

A strong risk factor, eh? That’s quite a statement. My height would not get me into the book of Guinness World Records, but, growing up, I was always the tallest girl in my class. Always. This did not make me happy, mind you. In all of my (Italian) school photos, I am always stuck in the back with the tallest boys. All of the other girls were much shorter than I. And, come to think of it, so were most of the boys. A nightmare, back then. I am now 1.73 meters tall, which I think is about 5 foot 7 inches. Do I qualify as tall? Not sure. And why is tallness a risk factor for myeloma, anyway? The study doesn’t go into that, unless I missed a crucial part.

At any rate, according to this study, you are safe from developing multiple myeloma if you are a short, fat or thin woman, OR a thin, tall or short man…

*The EPIC is a multicenter prospective cohort study designed to examine the association between nutrition and cancer. […] participants were enrolled from the general population between 1993–1998 at 23 centers in ten European countries: Denmark (Åarhus, Copenhagen), France, Germany (Heidelberg, Potsdam), Greece, Italy (Florence, Varese, Ragusa, Turin, Naples), the Netherlands (Bilthoven, Utrecht), Norway (Lund), Spain (Asturias, Granada, Murcia, Navarra, San Sebastian), Sweden (Malmö, Umea) and the United Kingdom (Cambridge, Oxford).

Eat your apigenin…

December 6, 2008 / / 1 Comment

In my November 30^th post I had a look at chemoresistance. Well, it just so happens that a few days ago, in a rather vain attempt to catch up on my Science Daily readings, I came across a bit of info (see http://tinyurl.com/56qhxh) that might be particularly useful to those doing chemo right now.

A recent study shows that apigenin, a naturally occurring dietary agent found in vegetables and fruit, can make cancer cells more susceptible to chemotherapy.

Here’s what happens: apigenin apparently localizes tumor suppressor p53, a protein, in the cell nucleus – a necessary step for killing the cell that results in some tumor cells responding to chemotherapy. […] In many cancers, p53 is rendered inactive by a process called cytoplasmic sequestration. Apigenin is able to activate p53 and transport it into the nucleus, resulting in a stop to cell growth and cell death. Now wait a sec. Why wouldn’t this phenomenon also help those of us who are not doing chemotherapy? Well, actually, I guess that would be implied in the researchers’ recommendation that fruit and veggies be included in everyone’s diet to prevent the development of cancer.

So where do we find apigenin? For the most part, in fruit (including apples, cherries, grapes), vegetables (including parsley, artichoke, basil, celery), nuts and plant-derived beverages (including tea and wine). It has been shown by researchers to have growth inhibitory properties in several cancer lines, including breast, colon, skin, thyroid and leukemia cells. It has also been shown to inhibit pancreatic cancer cell proliferation. Thumbs up!

If you do a search for apigenin on my blog, you will find my August 8 2008 post, reporting that this flavonoid doesn’t inhibit Bortezomib, which of course is a good thing for those who are on Velcade.

I did a quick online search on apigenin. Lots of interesting stuff came up, including a 2004 study (http://tinyurl.com/5o4lhw) on rats, which concludes that our body may be able to accumulate apigenin because it is metabolized, absorbed and eliminated slowly. So slowly, in fact, that apigenin was found in the rats’ blood nine days after administration. Incredible, huh? By the way, according to this study, apigenin can also be found in rosemary and camomile, and in honey, fennel and wheat germ.

In this November 2008 study (http://tinyurl.com/5sq5qt), we can read that apigenin inhibits NF-kappaB and also the molecules regulated by this transcription factor, such as Bcl-x (aha!) but not Bcl-2. It also inhibits COX-2. This is very good news for celery fans.

I haven’t been that interested in apigenin because, to my knowledge, there are no specific studies on apigenin and myeloma. But from now on I will try to keep half an eye on it.

Apigenin and leukemia: http://tinyurl.com/6hfgdk

Apigenin and ALL: http://tinyurl.com/5be38e

Apigenin and ovarian cancer: http://tinyurl.com/6qfooo

Apigenin and pancreatic cancer: http://tinyurl.com/6p3k9o

Apigenin and breast cancer: http://tinyurl.com/5qtva2

Apigenin and neuroblastoma: http://tinyurl.com/5ldg8o

The list goes on…

Chemoresistance, Bcl genes and supplements

November 30, 2008 / / 1 Comment

On November 13^th (see my “First steps” post) I revealed that I stumbled upon a sort of discovery. Well, it turns out that I hadn’t stumbled at all. I’d already mentioned this supposed “discovery” in previous posts. Sigh, I can’t remember everything I write, I s’pose. 😉 Well, anyway, since my “First Steps” post I have been doing some off and on research (so much to read, so little time…), and today I finally decided to post a few results, even though I still have to sift through a lot of literature. A seemingly endless task…

The “discovery” had to do with the antiapoptotic gene Bcl-x, which is related to Bcl-2 (=B-cell lymphoma 2) and has been linked both to tumour progression and chemoresistance. The overexpression of these two genes protects tumours from chemotherapy in many types of cancer, for instance in squamous cell carcinoma of the head and neck, or SCCHN (see: http://tinyurl.com/692n8b). Oh dear, there are so many studies on this topic but, in a nutshell, the Bcl family is bad news for all of us affected by cancer.

Chemoresistance, by the way, occurs when cancer cells are not affected by chemotherapy. They become immune to the attacks of these drugs. The consequence for chemoresistant myeloma and other cancer patients is obvious…I don’t need to spell it out.

Anyway, my starting point was a rather dated study, titled BCL-X Expression in Multiple Myeloma: Possible Indicator of Chemoresistance and published in 1998 in “Cancer Research” (abstract: http://tinyurl.com/69lxlz; full study: http://tinyurl.com/5wuyw7). Since it’s available for free online, I won’t go into too many details. But if you just read the Discussion part, you will see that Bcl-x is more likely to be detected in myeloma patients at relapse and correlates with chemoresistance. Bingo.

But let’s get to some potentially good news.

After skimming through that study, I googled the following words: “chemoresistance” and “myeloma.” One of the first links that popped up took me to one of Prof. Aggarwal’s many studies, the one titled Targeting chemoresistance in multiple myeloma cells by curcumin, quoted on the MMRF website.

This didn’t surprise me. I already knew that curcumin inhibits the evildoings of the Bcl family (there are heaps of studies on this). But then I wondered if there could be other natural plant extracts that inhibit it, too? The answer is a resounding YES! And, how odd!, I found all this info on my blog, just by doing a simple search. I hadn’t really made all these connections before now, and this made me think that I really must set up an Excel spreadsheet listing the specific targets of each supplement, in order to make some comparisons. For now, though, this is what I have found:

Bcl-2 inhibitors: nigella sativa (black cumin), gossypol, apogossypol, gambogic acid and omega-3.

Bcl-2 & Bcl-x inhibitors: curcumin, zerumbone, baicalein, resveratrol, ursolic acid, honokiol and capsaicin (=the “hot” stuff in red pepper). There may be others as well, but I stopped looking…for now. By the way, I have Pages on all of these extracts (see the right-hand side of my blog).

This bit of research has opened up a whole new world to me. And it also posed a good question: if I, with no scientific background and with only very meagre means at my disposal (a simple Internet connection), can…stumble upon a possibly useful connection/synergy between the natural and synthetic worlds, a connection that has the real potential to help cancer patients at the very least with the toxic side effects of chemo and possibly even with the treatments themselves (by making the tumour cells more susceptible to these drugs, e.g.), then why the heck don’t MORE cancer researchers devote MORE time to investigating this type of synergy?

I have answers, of course, but they only make me seethe. Eh.

To end on a happier note, I am having my bone mineral density test on Wednesday. This should be interesting…

Sherlock’s bone bulletin

November 27, 2008 / / 6 Comments

Sherlock is away on a business trip in Madrid right now (ciaooooo!) but sent me a quick note yesterday afternoon reporting on what our endocrinologist (henceforth, she shall be known as Dr. DF) had to say about her bone mineral density test results. Well, Dr. DF exclaimed that these results were so good that they seemed fake. I kid you not.

Sherlock explained that even healthy women nearing menopause lose bone density, so if you add myeloma to that equation, you can imagine what happens…nearing menopause + myeloma = dilapidated bone density. I just read online that we begin losing bone mass after age 35 and even more quickly after menopause. (Note: neither of us has hit menopause yet.)

But, contrary to all statistics and expectations, Sherlock’s bone density has increased in the past year and a half, a relatively short time, said Dr. DF.

Dr. DF excluded that this rapid increase could have been caused by Sherlock’s intake of vitamin D. Nope, she was really baffled. And that is when Sherlock brought up the curcumin and bone density studies. Dr. DF was intrigued and promised to have a look at said studies. So I guess I will be reporting more on this topic at some point next year. I have an appointment to see Dr. DF in February; the topic is bound to be mentioned.

They talked about me as well. Dr. DF commented that it was a terrible pity that I hadn’t had a bone density test before I began taking curcumin (indeed!). She said it would have been fascinating to see if my bone density had increased since then (hey, by the way, “then” = almost three years ago!).

Well, Sherlock has already begun badgering me, long-distance from Madrid!, about having a bone mineral density test…and, after giving the matter some thought yesterday, I concluded, “well, why not? After all, what’s another test?” Our results, Sherlock’s and mine, could be of use to other patients with bone issues. So I will make an appointment in the next few days.

For now, though, I just want to congratulate Sherlock on her excellent results. Bravissima!

Oh, and by the way, I forgot to mention that her haematologist (a different one from mine) pronounced her stable, too.

So…good news all around.

Haematologist appointment

November 26, 2008 / / 14 Comments

This morning I went to see my haematologist at the Haematology Center of Careggi Hospital in Florence. I hadn’t seen her since February of 2008.

One of the first things that she told me, smiling, is that she has begun recommending curcumin to her MGUS patients. And, she added, some of her patients read my blog (and have begun taking curcumin on their own). Well. To say I am thrilled is a huge understatement. Huge. But let’s proceed to what she said about my test results etc.

Not so good stuff

After examining my July test results (I still haven’t received my November ones), she asked me if I had had any colds, fevers or infections recently. No, I answered, not even a teeny tiny nose drip. I then asked her why she was so surprised to hear that, and she told me that my immune system is very very low (in Italian: Lei ha pochissime difese.).

She is concerned about the disappearing act of my good immunoglobulins (my IgMs and IgAs). She told Stefano and me that that is the only sign of possible progression. But this was at the beginning of our visit.

Well, I attribute my good health to the anti-viral and antibacterial properties of curcumin and, in part, also to a homeopathic remedy that Sherlock suggested I take last summer, which I believe protected me from getting my usual bout of bronchitis in the fall.

Incidentally, Stefano has had a horrible cold in the past few weeks, and I haven’t caught it. So I may have a disappearing immune system, but the little that is left makes the Ninja Turtles look like Turtle Doves (knock on wood! tocca ferro!).

Good stuff

She looked over my July spinal MRI results and confirmed what I already knew: I have no lesions (at least, not on my spine!). So we can postpone the series of full skeletal x-rays for now. Phew. No bone lesions. No lesions!

I asked her if she had obtained any details about my 2005 (=50% neoplastic cells) and 2007 (40% neoplastic cells) BMB samples, and she had. With a big grin on her face, she told me that the result is much better than expected: my 2007 BMB, taken about a year after beginning my curcumin protocol, wasn’t the reported 40% but LESS than that. Less than 40%? I almost hit the ceiling when I heard that bit of news!!!

She didn’t give me an exact percentage, though, and for some reason I didn’t think of asking her. I think I was too surprised and excited to think clearly right then. Duuuh! I should write her asking for more details about the BMB (BMB=bone marrow biopsy, by the way) samples at some point. Oh, another good bit of news is that I don’t need another BMB. Not in the near future. I took that as a really good sign, for it’s almost been two years since I had my last one. I hate BMBs with a passion, even though my 2007 one wasn’t as painful as the previous two (OUCH!), thanks to the experienced doctor who performed the procedure. Anyway, no BMB anytime soon. RELIEF!

I asked her if I am anaemic, which is a big concern of mine. Flipping again through my test results, she shook her head and said, “no, not at all.” She also told me which results I need to monitor for anaemia. So I will be able to do that on my own from now on. Fantastic! She did join forces with Stefano and insist that I eat more red meat. Okay. Okay. Okay. I will.

My monoclonal component has gone up a bit in the past year, which made her frown a bit, but she added that everything else is in such good shape that she isn’t concerned. This slight increase is not a sign of progression, in other words.

I told her that I was testing parthenolide now, and she was very interested in that. She told me that if it works, she will publicize my results. By the way, she wants to see my test results, the November 2008 and January 2009 ones, but she doesn’t have to see me again for six months. Yippee. Speaking of parthenolide, she told us that she is presenting a paper at the upcoming ASH Annual Meeting in December, and promised to keep me informed of any news about DMAPT (a week or so ago, looking through the ASH abstracts, I found a paper about DMAPT and myeloma, very exciting indeed).

I asked her about nifuroxazide, the oral antibiotic used to treat colitis and diarrhea, which has been found to kill myeloma cells by directly inhibiting STAT3 (see the September 29 2008 issue of “Blood.” I have the full study and will report about it soon on my blog). She knew about the study but had nothing to add. None of her patients are taking it. She seemed a bit ho-hum about it.

At the end of our visit, Stefano and I asked her what the verdict was. She answered.

STABLE

P.S. As I typed that word, “stable,” tears filled my eyes. In fact, I had to stop myself from sobbing. Where the heck does all this emotion come from? Well, I guess a part of me was scared, since my July results aren’t that splendid…but I can relax now. No need to worry. My specialist confirmed that I am stable. That’s cause for celebration, not tears.

Oh, one last thing: As we were about to leave, she told me to listen to my body. No kidding. I was a bit surprised, since she is, after all, a conventional specialist. But one who can think outside the box.

She has earned my utmost respect.