Dendritic cells, miR-29b, and multiple myeloma

November 30, 2017 / Margaret / 1 Comment

Life is very complicated these days. This morning, after consulting with the vet, I discovered that our giardia-ridden kittens will have to undergo a second cycle of treatment, which will begin next week. This means that they will have to spend another month holed up in their luxurious quarantine, poor dears! I am spending almost all of my free time with them…playing with them, feeding them, holding them, cleaning up, sterilizing, and being SUPER CAREFUL whenever I handle anything at all in the quarantine room.

Mind you, it may sound like it, but I’m not complaining. Not at all!!! I mean, just look at that face! 🙂

Well, okay, I admit, I HAVE had a few frustrating moments in which I’ve asked myself, and/or Stefano, HOW and WHY did we get into this mess??? Agh!

But the truth is that we almost certainly saved the lives of our kittens, and probably the lives of their siblings, too (immediately after we received the giardia diagnosis, I got in touch with the woman who gave us the kittens…She had no idea…). So that is something to remember…

And besides, these two kitties are so incredibly adorable and funny and affectionate…They act like normal, playful, curious, crazy kittens that zoom all over the place and then crash and sleep until they have enough strength to go back into the crazy kitten mode…I mean, you can’t tell that there’s anything wrong with them…except for the huge quantity of smelly pooparoni (though it’s MUCH better than it was a couple of weeks ago, let me tell ya)! Yuck!

Okay, enough…It will only be another month, then they’ll be cured, and we’ll be able to let them out into the rest of the house…and meet their older siblings (yikes…a bit nervous about that). If we’re lucky, they’ll be well enough by Xmas. That would be a lovely present indeed!

But that’s not the reason I’m writing this post, even though, hehe!!!, it might seem that way. Nope, this evening I wanted to write (then I got derailed, sorry!) about a new myeloma study that I bumped into just this morning…a very interesting, and mostly Italian!, study on myeloma and dendritic cells (DCs, for short), which is fully available online and has been accepted for publication in “Leukemia.” Here’s the link: goo.gl/wFMjS1 I’ve written a few posts on dendritic cells and myeloma, btw, so you can use my “Search Box” to have a look through my blog, if you want.

The abstract begins with a good explanation of DCs: “Dendritic cells (DCs) play a key role in regulating tumor immunity, tumor cell growth and drug resistance.” The authors believe that MM cells may recruit and reprogram DCs in order to survive. They found a member of the microRNA family (a family of teeny tiny RNA molecules that regulate gene expression), called miR-29b, which is is not downregulated in normal DCs but, drum roll!, is downregulated in most types of cancer, including myeloma.

Now, even though we may not understand (or care!) what exactly this little, hairpin-shaped miR-29b does, etc., the main thing is that it is able to counteract “pro-inflammatory pathways, including STAT3 and NF-kB, and cytokine/chemokine signaling networks which correlated with patients’ adverse prognosis and development of bone disease.”

Translation: more miR-29b, less myeloma cell proliferation.

So, miR-29b is GOOD. From our perspective, of course, not from that of a myeloma cell. 😉

Now, it’s getting late over here in Italy, and I don’t have much time left. Stefano is on his way home (oh, oops, he just walked in the door…I have to go help him with dinner…He’s the chef tonight…). So I have to leave you with this study and all its complexities.

But do have e a look at page 23. There you will find that ASPIRIN and CURCUMIN “revealed a promising therapeutic activity in both MGUS and sMM patients.”

AHA!, so researchers ARE paying attention. This one sentence made my day…my week, even! 🙂

Oh, and guess what? Curcumin upregulates the expression of miR-29b. Tadaaaaaa!

I will have to keep my eye on these authors who are also looking into the role of this little molecule in the progression from MGUS to MM.

Good stuff, good stuff!!! Take care, everyone!!! Ciao!

Giardiasis

November 22, 2017 / Margaret / 3 Comments

Well, phooey! Last week we finally found out that our two new kittens have giardiasis, which is an intestinal infection caused by a parasite–giardia (see photo below…it looks like a harmless balloon with a scary face, but it’s actually a microscope image of this nasty little intestinal parasite)–which can be transmitted to humans, too, especially, eek, those with an immunodeficiency.

Eh. I have to be super careful. And I have been…

How we found out about the giardiasis is a long messy (and smelly!!!) story that I’ll spare you. Luckily, the kittens have responded well to the anti-giardia drug and are in excellent shape now, gaining weight and so on. They are even more adorable and vivacious and funny, now that they are (obviously) feeling better.

Many thanks to the lovely vet who, after others failed (no comment!), finally figured out what was wrong…and carried out the correct test, the giardia test…GRAZIE!!!

So all is well and relatively calm in our feline household. I say “calm,” because Pandora and Pixie have not yet been released from their quarantine area (i.e., the guest bedroom, which, stuffed with all the presents that friends and neighbors have brought over, now looks even more like a kittens’ Disneyworld…Indeed, I’ll have to donate some toys to the cat shelter at some point…).

Unfortunately, we will probably have to keep the two kitties under lock and key for another couple of weeks or so, until we’re sure that the giardia beasties are all gone for good…Bummer, eh! But, better be safe than sorry!

As you can imagine, taking care of the kittens in this period…doing laundry, disinfecting their room, disinfecting ourselves, making sure they are happy and playing a lot, doing more laundry (!), and so on and so forth, has REALLY cut into my free time, so I haven’t finished my almost-ancient-by-now post about the EBV-MM link. That annoys me because it’s a very interesting post, to boot, so I will try to finish it in the next couple of days.

That is…if nothing else comes up! Aaaaghhhh! 🙂

Take care, everyone! Ciao!

Pandora and Pixie-Panacea

November 9, 2017 / Margaret / 2 Comments

For the past seven days I’ve been dividing my free time between our two new kittens and our resident adult cats.

The two “groups” haven’t officially met yet, because the kittens have loose stools (not caused by parasites, luckily…so it’s probably just because of the dietary change…still, quite gross…and smelly, yuckaroni!!). We have to get rid of the kittens’ intestinal problems before letting them,er, loose in the house. I mean, it’s one thing to have TWO cats with intestinal issues, quite another to have SEVEN cats with issues. Ouch! So they are in quarantine in the guest bedroom.

Of course, my adult cats KNOW that something fishy is going on behind that closed door. They can certainly smell and hear the kittens, especially when the tiny critters run around the room, chasing each other and making quite a bit of noise.

But they haven’t actually SEEN them yet.

I’ve transformed the guest bedroom into a kitten wonderland. It’s packed with our cats’ old toys and stuffed animals, and with NEW toys, too! Most of our friends and neighbors who have come to see the new kittens have been bringing them NEW toys…so we have some new kitty tunnels and kitty wands. I’ll have to donate some to the cat shelter at some point!

Anyway, these two little sisters are the friendliest kitties we’ve ever had, with the possible exception of Pinga, our 8-year-old, who also made herself at home immediately. But Pinga isn’t always super friendly with strangers, whereas these kittens absolutely love and climb all over everyone who comes to visit. They are super kittens, simply bursting with joy. You can’t help but smile and laugh at their antics. 🙂

They have made such a difference in our lives…in just one week! Yes, sure, right now they’re a lot of extra work, keeping the litter box clean, cleaning the floor (little creatures are very messy!)…

Plus, Stefano and I aren’t sleeping together, which is hard for both of us. He sleeps with the kittens, I sleep with the adult cats. It has to be that way until we let the kittens out of that room. But it won’t be for long. As soon as there is no more diarrhea, we will slowly and carefully introduce the adults to the babies.

Now for their names: Pandora is the mostly-white kitten. She is VERY energetic, playful, mischievous and, well, all over the place. We have named the multi-colored kitten Pixie-Panacea (Pixie, for short; Panacea, the goddess of healing, was suggested to me by a few blog readers…thank you!). Pixie is much calmer and cuddlier. She’s also slightly smaller than Pandora, and not as tough.

I’m still finding it difficult to get decent photos of them, because when they play, they play hard and fast, especially Pandora, and all my photos come out fuzzy. Terrible. And yes, I should have “lightened up” a few of these photos, but I don’t like altering photos. Anyway, I’ll see what I can do with the next photos I take (I take heaps every day, actually)…

These are the most adorable kittens I have EVER seen! And they’re OURS! Such happiness…after so much sadness…Life is good…again! 🙂

“Gut bacteria ‘boost’ cancer therapy”

November 4, 2017 / Margaret / Leave a comment

That’s the title of a very interesting BBC News article I read this morning, thanks to my friend Paul: goo.gl/pkXS1J It’s about two recent studies that examined patients with cancer (1. lung or kidney; 2. melanoma), discovering that those who had a lot of “friendly” gut bacteria responded better to immunotherapy.

Excerpt: Dr Jennifer Wargo, from Texas, told the BBC: “If you disrupt a patient’s microbiome you may impair their ability to respond to cancer treatment.”

Okay, so the patients in the two studies didn’t have myeloma. But I would bet anything that those three types of cancer aren’t the only ones that are strongly impacted by our gut bacteria. I would bet anything that myeloma is on that list, too. Anything!

Besides, I then read (while cuddling my black kitty, Prezzemolo, in my arms) that the gut microbiome really changes after a stem cell transplant. See this 2015 Italian study published in “Blood,” e.g.: goo.gl/Xn12JC

Changes in the gut bacteria of SCT patients can cause severe infections and inflammatory bowel conditions…and also the scary and horrible GvHD (graft versus host disease).

A 2015 U.S. study focuses on the role of Clostridium difficile (a really nasty sort of bacteria, as the word “difficile” implies!) during SCTs: goo.gl/AK5yQp. It concludes that C. difficile is one of the main causes of lower gastrointestinal distress in patients undergoing autologous SCTs. Yep, myeloma patients, too.

In sum, if you have too much bad bacteria, you can get into serious trouble…even if you’re healthy!

C. difficile, incidentally, really proliferates in the colon after we use antibiotics…So whenever you’re on antibiotics, make sure you also take probiotics (not at the same time, eh!). Of course, always ask your doctor first…

I’ve said it before, and I’m saying it again today: we really need to pay attention to our microbiome.

Even if we aren’t on antibiotics…

Our body needs probiotics.

Pixie, Pandora, Peppola, Pepper…???

October 31, 2017 / Margaret / 3 Comments

Stefano and I went to visit our new kittens about ten days ago. Oh my. They are so unbelievably ADORRRRRRABLE…such wonderful, happy, friendly kittens…

They are still with their mother, and in fact here is an important bit of information: kittens should NOT be taken away from their mother before they are at least two months old, otherwise they might have behavior and even health problems later on in life. And so we have been waiting for them to be weaned and reach the proper age.

It also turns out that our rather random decision to adopt TWO kittens instead of one was absolutely spot on. Kittens that are adopted in pairs tend to be healthier and happier and have better “social skills.” Yay!

In the beginning, we’d decided to adopt two of the three females in this 4-kitten litter. But the little male (see photo on the right) chose us as soon as he set eyes on us…It was so obvious. He was “in our face” all the time (during our first visit and, even more, during our second visit, climbing up our jeans, etc.).

And so we both ended up falling completely in love with him. So, after the second visit, we decided to adopt him and the little white female. We were going to call the male “Potter” as in “Harry Potter,” since he cast a big spell over us. Plus, we’re both big fans of HP! 🙂

But before we could tell the kittens’ human mother (signora Carla), she gave “Potter” to a little boy who had just lost his Dad. He came over to her house to see the kittens with his mother and brother, and he asked if he could have one. Carla didn’t know, at that time, that we’d changed our minds about “Potter.” And so, of course, she gave him to the sad little boy. We found out the same day. Stefano was very upset, and I admit that I felt a twinge of sadness, too…but, after a moment, I thought, “well, that little boy needs an amazing super kitten more than we do. And our two little girls will be just as wonderful…for sure!”

So, no regrets (although, okay, Stefano is still a bit upset…).

The little mostly-white female (photo no. 1) has a HUGE personality. So we may name her Pandora or Pixie. Any other “P” names that make you think of a feisty and totally lovable little creature like that? As for the darker, multi-colored kitten (photo no. 3, sitting next to her sister on my lap), she was asleep most of the time, so we aren’t sure about her name. In fact, we’re not sure about what to name either of them.

I tried to take some decent photos of the tiny tornadoes during the second visit, but they were either climbing madly all over us, chasing a bit of ribbon that I’d brought with me, or way too close to the camera. These are the best of the lot. Pandora/Pixie/? is on my crossed legs in photo no. 1; Potter is on Stefano’s in no. 2, and No-name-at-all-yet is out of focus in no. 3.

Anyway, TOMORROW (can’t wait!!!) we’re picking them both up and bringing them to their new home, so I’ll be taking PLENTY of photos in the foreseeable future…good ones, or, at least, better ones! 😉

As for the virus-myeloma post I’ve been working on lately (a long, complicated article), a few days ago I almost had a heart attack, when the bloody Word file wouldn’t open. I kept getting the “this file is damaged” message (or something similar). I finally figured out how to fix it, but boyohboy that was scary. From now on, I guess I’ll save my work in a couple of places, just to be safe. Anyway, with the kittens coming, I don’t know when I’ll get back to it…but I hope to finish it soon (while they’re sleeping or with Stefano, e.g….).

Take care, everyone! My mind is full of kittens right now, and nothing else!!!

Ciaoooooo! 🙂

The connection between EBV infection and MM and MGUS

October 19, 2017 / Margaret / 6 Comments

Today’s short post deals with proof of the association of the Epstein-Barr virus with MM and MGUS, which I found in a 2016 University of Sassari (Italy) study.

The full study isn’t available for free online, but, thanks to a lovely friend, I was able to get my hands on it. If you click on the page (at the following link), thereby enlarging it, you will be able to read almost the entire first page of the study where most of the results are posted, actually: goo.gl/b8Tx3F

The study points out that until now, apart from a couple of case reports on plasmacytomas possibly caused by EBV in immunodeficient MM patients, there has been only ONE STUDY on the possible association of EBV and MM. That study, which I am going to have a look at soon, found traces of EBV DNA in the bone marrow of MGUS and MM patients. Eh!

But this 2016 Italian study is the FIRST one to really make the connections. Click click click.

I won’t, indeed cannot, go into too many other details, for reasons of copyright, but I can report this bit of information, since you can see it for yourselves on the page at the above link: the patients were either MGUS or in different stages of MM. And they were IgG-kappa, IgG-lambda, IgM-kappa, IgA-lambda.

The study results show, for the first time ever, a connection between MM and MGUS and the Epstein-Barr virus.

And they also show that EBV may contribute to the survival of MM cells. How?

The researchers found that the latent EBV LMP2A gene was overexpressed in both MM and MGUS patients. Among other things, this gene activates the RAS pathway (do a search of my blog for more info on RAS), which is very bad news for us…but very good news for MM cells.

In short, the blasted gene helps MM cells survive…

Okay, I feel a bit like a dog with a bone right now. More chewing needed…more research, more studies…I have a few on my desktop, which I hope will yield some useful information…

Please feel free to leave me a comment, by the way. I’d love to hear, in particular, from those whose MGUS, SMM, or MM was diagnosed after some sort of viral episode…EBV, HCV, etc. Tell me/us your story! 🙂

Thanks so much! Ciao!

Update on the viral connection to myeloma

October 18, 2017 / Margaret / 3 Comments

A blog reader (thank you!) sent me the link to a French study that was recently published in JCI. It discusses the link between IgG myeloma and pathogens such as, ta da!, the Epstein-Barr virus, or EBV for short, the virus to which I was exposed while doing my doctorate at the University of Toronto and which I have always believed to be the underlying cause of my own, er, situation…

Before I forget, in all the excitement!, here’s the link to the (full) study: goo.gl/g73Sx8 And there, right at the end of the abstract, we learn that “a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients.”

Bingo!

This isn’t the only study I’ve read or glanced at in the past week on pretty much the same topic, which, um, to be honest, I haven’t looked at in years now. So yes, there are others. But first, let’s have a look at this one.

The abstract tells us of the association between B-cell malignancies and EBV (also, HCV and H.pylori): “Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori.” First point.

And here is another piece of the puzzle (see Introduction): “…viral and bacterial infection in patients can lead to the production of oligoclonal or mc Ig.” (Note: mc Ig = monoclonal immunoglobulins or antibodies.) Our clonal plasma cells produce a lot of these antibodies that thus far had been thought “not to have functional activity.”

But wait!, that may not be the case. Perhaps these antibodies do have a purpose after all. In previous studies, the French researchers in fact found that in Hepatitis C-positive patients these antibodies “almost always target the virus…” Aha. And that is an important third point. I don’t remember ever reading anything about MM cells doing anything remotely useful, so this was a big, no, it was a HUGE discovery for me.

Let’s keep going.

Their conclusion is that “an abnormal plasma cell response to infection could be the initiating event of some MGUS, SM, or MM cases.”

I can’t tell you how this made me feel, after years of having myeloma experts tell me that there could NOT possibly be any link whatsoever between my myeloma and my EBV infection. Vindication? Yeah, I guess.

The article at one point refers to a study discussing the case of a patient with a chronic HCV infection whose stage IIA MM regressed to MGUS.

Regressed to whaaat??????

Now that really caught my attention!!!!!!!! And so I rushed to read the case study, which is fully available online and is an Italian study, to boot: goo.gl/yeDwZvZ

This patient’s MM regressed to MGUS after just six months on an anti-HCV treatment. Six monthsssssss, that’s it???

I had to stop reading for a minute to let this all sink in.

How did I miss that 2013 Italian study???

Well, true, I can’t keep track of everything…I do have a life, after all!!! Besides, the important thing is that I finally did read it. Anyway.

So here’s the thing: IF transforming her MM back into MGUS was possible for an HCV patient, why couldn’t, theoretically, the same be possible for an EBV patient with SMM or MM? And even if a regression didn’t occur, what’s there to lose?

Get rid of the virus, get rid of the myeloma. Sounds simple. Too simple, probably. But…worth a try. (Important note: I don’t know how toxic the antiviral treatments are. More research AND my doctor’s advice needed, here, before doing anything too hasty…)

Now, as the authors suggest in the Discussion part, perhaps this could be feasible in the early stages of the “chronic underlying infection”…But they also add that it might even be effective in later stages of MM. Boy, that would really be something, wouldn’t it?

Here are some excerpts from the Discussion (my highlights): “Overall, our findings imply that chronic stimulation by infectious Ag may promote MGUS and MM in certain patient subsets. Importantly, some of the identified infectious pathogens (HSV, HCV, H. pylori) can be effectively treated. This observation has obvious clinical consequences, since the detection of MGUS or SM patients with an mc IgG specific for a treatable pathogen would allow the proposal of antiviral or antibiotic treatment for patients. If an underlying chronic infection were cleared early enough in disease progression, it could perhaps offer the tantalizing possibility to prevent MGUS transition towards SM and overt MM for the first time. In such cases, addition of antiviral or antibiotic treatment to current protocols might indeed induce disease regression and/or improve response to standard treatments, as reported for interferon-? treatment in HCV-associated MM.”

Hmmm, they say that “some of the identified infectious pathogens […] can be effectively treated,” but they don’t list EBV. Have to check on that one…

Okay, I’m stopping here for today. This is just the first part of a series of posts that I intend to write on this topic. I’ll re-read and, if I find something else of interest, finish writing about the JCI article in my next post…in any case, I have also downloaded a couple of other studies that might be of interest. Need more time, though…

Must rush off now. Ciaooooo!

Oh wait, let me leave you with some food for thought, hehe: curcumin inhibits EBV.

Bam!

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Author: Margaret