Galectin-3 inhibitor

[leswell]

Is anyone aware of current trials in the US for Galectin Therapeutics’ GR-MD-02 for advanced prostate cancer patients? Have any of you tried this or are you considering it?

[pjoshea13]

This will not answer your question, but I have been interested in (& confused by) galectin-3 for 13 years.

First there is the literature om MCP (modified citrus pectin).

The earliest PCa paper dates to 1995! [1]:

"Modified citrus pectin (pH-modified), a soluble component of plant fiber derived from citrus fruit, has been shown to interfere with cell-cell interactions mediated by cell surface carbohydrate-binding galectin-3 molecules."

The idea is that by gumming-up galectin-3, circulating cancer cells will not be able to dock or clump. i.e. MCP might be able to prevent mets.

Secondly, there is the question of galectin-3 expression in PCa.

[2] (1995) - MD Anderson:

They used tissue from: "seven normal human prostates, eight cases of prostatic intraepithelial neoplasia (PIN), 20 primary adenocarcinomas of the prostate, and 12 prostate cancer metastases"

"... galectin-3 expression was significantly decreased in primary carcinoma and metastatic disease compared with normal and premalignant tissue."

"We conclude that loss of galectin-3 expression may be associated with the progression of prostate cancer."

[3] (2000):

"Galectin-3 is a carbohydrate-binding protein whose level of expression has been shown to be correlated with metastatic potential in a number of different tumor types."

"These data demonstrate that galectin-3 is downregulated in prostate cancer."

[4] (2007):

"... gal3 promoter was highly methylated in human prostate cancer tissue but not in normal tissue."

i.e. in PCa, the promoter region for galectin-3 is likely to be silenced via methylation.

This could be because galectin-3 has an anti-cancer role when situated in the nucleus. [5]

[6] (2009):

"The expression of the gal3 was found drastically downregulated in advanced stages and, interestingly, mostly in the cytoplasm. On methylation analysis, the gal3 promoter in stage II prostate adenocarcinoma (PCa) was found heavily methylated, whereas in stages III and IV, it was only lightly methylated. However, in stage I PCa, both heavy and light methylations were observed in the gal3 promoter."

[7] (2013):

"This is the first study that showed a decreasing gradient of Gal-3 expression in benign, adjacent-benign and tumor tissues."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/785...

[2] ncbi.nlm.nih.gov/pubmed/105...

[3] ncbi.nlm.nih.gov/pubmed/108...

[4] ncbi.nlm.nih.gov/pubmed/174...

[5] ncbi.nlm.nih.gov/pubmed/153...

[6] ncbi.nlm.nih.gov/pubmed/197...

[7] ncbi.nlm.nih.gov/pubmed/228...

[BigRich in reply to pjoshea13]

Patrick,

A few years back. I looked at MCP it seem a valuable PCa add on. However, the research gave me pause regarding my kidney disease or me being a diabetic. I can't remember what the issue was? Do you know why a person with these coditions would have pause?

Rich

[pjoshea13 in reply to BigRich]

Sorry Rich, - no idea. -Patrick

[leswell in reply to pjoshea13]

Patrick,

We should have known you’d have the answers! We had no idea there was such a long history of Galectin-3. There’s much to read and learn from as always in your well-researched reply which will interest and, we trust, help many.

For Leswell, even following the pending orchiectomy, our question remains,”Why not Avodart and Proscar? Why not GR-MD-02 (if it’s ever available)? With T and DHT still being produced other than by the testes, there’s no reason to surrender the fight.

With continuing curiosity, hope, and much gratitude,

Les and Jan

P.S. Les is in the garden. Since he’s the writer, I should have him edit this before hitting SEND. Oh well. Back to my red peppers.

[leswell]

Oops. Missing quotation mark.

[leswell]

Written September 30, 2017, at 2:27 PM

Dear Patrick and Nal,

Beets are roasting, and Les is out once again, this time to remove the immature squash and blossoms and in doing so manipulate the nearly ripe Sunshine squash to begin curing on the vine. How different is that from taking Modified Citrus Pectin to clog up the AR receptors? We’re messing with “Mother Nature.” Heady stuff.

During lunch I read your posts to him; he sends good wishes and thanks—except for the shocking price of the MCP. Understand, his preacher father’s parishioners used to pay him by tucking pieces of meat between the storm and entry door where they were discovered after the morning service.

Without permission from the fiscal conservative of our family, I’ve ordered 454 grams of Econugenics Pectasol C Modified Citrus Pectin from Amazon. He’ll copy your dosage, Nalakrats, (as he has several times already) and start with 5 grams, three times daily.

I am aware of the complexity and reality of angiogenesis and anti-angiogenesis having conducted endless computer searches in 2002 when my brother (married to Les’s sister) was treated at Mayo for an aggressive brain tumor. Jim didn’t want to go to Duke as I recommended but to stay at Mayo and close to their home in Northfield. He probably made the right choice; Duke’s best efforts couldn’t make Teddy Kennedy survive his terminal diagnosis any more than Mayo could my brother’s.

One more too personal note about your family in Israel. My father was the pastor of a Twin Cities church which gave him and my mother the gift of a trip to Israel. How they loved and often referred to that trek about the country with friends. I still have boxes of slides Dad took. My mother, of course, hoped to evangelize the non-Christians. She couldn’t even convince my Jewish sister-in-law who fully understood what my mother was up to. What can you expect from a Baptist minister and wife? Dad became one after managing a steel business in Waukegan, IL, and teaching math in Seattle and at Minnehaha Academy. (These days the entire US is aware of my family’s high school—yet another tragedy.)

Les thinks I should delete the non-medical half of this, but I’m not starting over. I replied that I’ll stick to the medical stuff in Heaven.😇

Thanks again.

Mrs. S

P.S. I’ve begun distinguishing a few of you in Health Unlocked with your own colors in Google Keep. Patrick, you’re green, Dan is yellow, Nalakrats purple. To be continued. Back to reading those PubMeds at 7:30 p.m. Or maybe I’ll watch an episode of the Icelandic “Trapped” on Amazon. If questioned, tell the administrators that even Sam Sifton of the “New York Times” doesn’t write ONLY about cooking. If you ever want to talk about that...

[BigRich]

Nalakrats,

Do you know of any reason a person with hypertension, kidney disease, A-Fib, being a diabetic, and having PCa would not want to take MCP, because of its impact on their medications or conditions?

Rich

[leswell]

Well put. Never fear. We don’t hold anyone responsible but ourselves. I do think Les is feeling better on the combination of supplements he’s taking at present: Metformin, BioResponse DIM, Vit. D3, Super K, Country Life’s Calcium Magnesium complex, and B12 injections. Lupron is another matter, a mixed blessing putting it mildly. Chemotherapy was survivable. What was most our fault is not having regular physicals. It’s too late now, but we’ll continue to act as if it isn’t. Go well. We heed all your warnings. Mrs. S

[BigRich]

Vasotec,atenolol,simvastatin,doxazosin mesylate,rapaflo,lasix,aspirin, lupron, VitaminD3, magnesium, Zyflamend.. Next month, I hope to ass Zytiga and metformin.

Rich

[leswell]

I’m not an out-loud pray-er, but if prayer is the heart’s sincere desire, ours include all of you daily.

So, Nalakrats, here is my preliminary schedule for Les regarding the MCP.

Coffee and toast whenever he awakens and puts it on be it 3, 5, or 7 a.m.

MCP at 9 a.m.

Main meal with additional supplements at noon.

MCP at 3 p.m.

Light supper with red wine at 6 p.m.

MCP before retiring which is usually between 9 and 11 p.m. for him. Later for me if I’m writing to the family or the likes of you.

Let’s see, D3 and K and Metformin all taken with food. Easy. Cal/Mag also with food but not with the D3 and K. Also easy.

These are self-imposed mini-fasts throughout the day. Also probably good, but Les still loves to eat, and I like bringing him treats. Also good, but he still likes carbs, toast especially. Not so good.

I like a challenge. I also appreciate your specificity. We’ll let you know how it goes. Now here comes Amazon with the MCP on a drone after midnight. Just kidding. They deliver mighty speedily, however. My youngest brother is working on his latest invention, this time it might relate to a fine film of a battery—for drones? That’s hush hush. From robotics (his biggest success)to LED bulbs designed with another brother which included numerous trips to China. Who knows what’s next? He never sleeps. Speaking of which, goodnight to you and yours.

Thank you.

Mrs. S

[wifeofvet]

my husband took massive amounts of this form of pectin in the beginning after his gleason 10 diagnosis with mets to the rib...along with every other supplement that even hinted of being of benefit to PCa. he still only got 5 years out of casodex before disease progression, just as his doctors had predicted he would.

[leswell in reply to wifeofvet]

Good morning, wifeofvet,

Leswell is up putting on the coffee. The MCP isn’t here yet, so we don’t have to worry about the med schedule for another couple of days.

Thank you for replying to my question. I’ll try not to wander off topic.

I don’t know why Les wasn’t given Casodex. (His PSA at diagnosis was 1500, GS 7 + 9.) Our oncologist was going by the NEJM’s recommendation at the time for early chemotherapy combined with Lupron, a decision which resulted in a PSA of 2.82. He’s continued on leuprolide after chemotherapy until today with one three-month vacation, and the PSA has been up to 169 and back to 21.97.

Five years sounds wonderful to us! Maybe the MCP he took initially did contribute to his “life extension”? We all need more evidence from the current Phase III trials. Nevertheless, we’re not waiting. As you’ve probably noted, we’ll read the instructions and follow Nalakrat’s recommendation for taking it without food and two hours from other supplements. Did your husband do that? Did he have any side effects? Above all, how is he?!

Mrs. S

[wifeofvet in reply to leswell]

my husband was diagnosed in 2005. clinical trials for high dose docetaxel were just beginning. Casodex was the only drug available at the time along with Lupron

[leswell in reply to wifeofvet]

P.S. Thank you both so much for your service to our country and to us!

[Dan59]

I tried search, as you can at clinicaltrials.gov for prostate cancer and galectin and came up with nothing, You can go to the clinicaltrials.gov page and see what you come up with

[leswell in reply to Dan59]

Good morning, Dan,

I will do that. Nalakrats says there are Phase III trials in both Israel and the US, but I don’t think he said where the trial is taking place in our country.

Btw, I wrote a letter to you after your return from Alaska and while trying to download a couple of photos (I know better.) lost the short note. For now, just know you are in both our minds often as you and we are making important decisions about continuing treatment. Until later, Les and Jan

[Dan59 in reply to leswell]

Les, and Jan , Thank you. I thought Patricks and Nalakrats response was very excellent, I am glad we have some smart guys in this group, You are both in my thoughts and prayers. Had a great time in AK, will post pictures as I go.

Dan

[leswell in reply to Dan59]

Dan,

Not doing too well here in the search.

Below are a couple links to MCP studies. That substance is being re-examined closely, e.g. Yale Cancer Center in August. I’ll check out Haifa, Israel, too. Mrs. S.

Googled—

NIH Phase 3 trial of Modified Citrus Pectin 2017

And from clinical trials.gov two recruiting trials in Portland (not for prostate cancer) are:

Galectin Inhibitor (GR-MD-02) and lpilmumab in Patients With Metastatic Melanoma

GR-MD-02 Plus Pembrolizumab in Melanoma, Non-small Cell Lung Cancer, and Squamous Cell Head and Neck Cancer Patients

———

Sorry I couldn’t just send copies of the photos I took of these links, Dan. We will have to ask Nalakrats which US trial he had in mind. And now for the MN Vikings.

[BigRich]

Thank you for your sage advice. You have wisdom with age.

Rich