The Sonic Hedgehog-Induced Type 3 Deiodinase Facilitates Tumorigenesis of Basal Cell Carcinoma by Reducing Gli2 Inactivation
Cristina Luongo,* Raffaele Ambrosio,* Salvatore Salzano, Andrzej A. Dlugosz, Caterina Missero, and Monica Dentice/.
includes various hedgehog revelations such as :
Type 3 deiodinase (D3) inactivates T3 via specific deiodination reactions. It is an oncofetal protein frequently expressed in neoplastic tissues and is a direct target of the sonic hedgehog (Shh) pathway ........
Vertebrates possess 3 hedgehog (Hh) proteins, sonic Hh (Shh), Indian hedgehog (Ihh), and Desert hedgehog......
Hhip [hedgehog interacting protein]
and more interestingly :
"Topical TH treatment with a T3-containing cream reduces BCC tumor growth in vivo
We hypothesized that the local hypothyroidism determined by D3 overexpression is a condition that facilitates BCC cell proliferation. To determine whether T3 could be effective in affecting cell growth in an in vivo context, we evaluated the efficacy of using topical T3 for the treatment of spontaneously forming BCCs. To this aim, we used a mouse model that specifically overexpresses Gli2 in keratinocyte epidermal compartment (K5-Gli2) and develop multiple BCC-like tumors (20, 31). In this animal setting, we tried to counteract D3 action within the tumoral cells by topical T3 treatment. Interestingly, the BCCs treated with 300nM T3 grew much slower (tumor volume was 2.7-fold reduced) than vehicle-treated control tumors (Figure 3). This result indicates that in an in vivo setting, T3 reduces tumor growth of spontaneously forming BCCs."
tagging jimh111 in case you're interested in the T4/T3 cancer aspect of this study for your list ..
Thanks (I think). I don’t understand Sonic Hedgehog signalling nor the role of Kisspeptin which is something to do with fertility. I think the researchers are having fun with names.
Recently I’ve mused on the concept that cancers are like viruses, they are both cellular things that replicate and both exploit mechanisms that help them. I think this is why vaccines offer great potential for future cancer treatment. By the way, Dr Skinner proposed that cervical cancer was caused by a virus. Sadly he picked the wrong one, he thought it was herpes virus. The chap who identified HPV as the villain got the Nobel Prize.
T3 has been used effectively in one trial to treat cancer, this worked by enabling lower fT4 levels. I think I’ve seen a study that showed a direct effect of T3 reducing cancer growth (it might have been this one). This is specific to one or two cancers not a general thing. For example higher T3 (or T4) levels promote breast cancer.
I have to say my Oncologist wanted my Ft 4 & Ft3 high when I went through BC treatment. Not low like the private Endocrinologist wanted and he was horrified at her recommendation and said we are not doing that! He was right It certainly did not promote growth of my BC but it did get me through a long trying aggressive treatment period.
It has left me wondering how accurate this idea of low thyroid levels is a great idea when treating cancer.... Was it based on some research on cancer cells as opposed to whole people with cancer? Not doubting the research says it Jimh111, just the context.
Breast cancer is an umbrella term and am always suspicious when it's used generically.
Different forms of BC respond differently and need treatment designed specifically for this reason. This is called typing and since they have been doing this far more effective treatments have evolved for specific types. Sometimes of course the cancer may contain multiple types as mine did.
I think my Oncologist point of view was that my body needs to be strong to cope with the medicine so to speak but if you lower thyroid hormones the body will struggle, be weakened and struggle even more in treatment and so the body will not be able to fight, cope with the drastic effects of treatment and the cancer will take over.
Funnily enough the surgeon had the same opinion and was horrified at the idea of lowering my thyroid levels. He said it was a nonsense and to not do it.
Overall I had the impression that neither thought greatly of the Endocrinologist. The NHS Endo I then saw clearly agreed with the Cancer team and said carry on same level of treatment as before diagnosis. I was very grateful to him. I stayed on his books till he retired several years later. 9yrs on still in remission still on the same dose of thyroid hormones as before treatment.
Since treatment interestingly enough I discovered am Coeliacs and PA. Maybe the cancer was a consequence of my body being so out of balance.....misfunctioning to such a degree that it messed up on its cell generation... There's no research behind this that I know of just me wondering... 😊
like everything thyroid hormone related , the answer is going to be " it's complicated"... and very specific to the particular type of cancer.
the related paper (at the bottom of my post) about Squamous Cell Carcinoma ~"Thyroid hormone induces progression and invasiveness of squamous cell carcinomas by promoting a ZEB-1/E-cadherin switch" ~ seems to be saying that thyroid hormone initially has a protective effect , but once the problem has started , then thyroid hormone has the effect of making things worse .
"Taken together, our in vitro and in vivo experiments revealed that the effects of D2 and D3, and consequently, TH action, are uncoupled to the various phases of cSCC tumorigenesis. Indeed, while TH initially reduces tumor formation, it subsequently accelerates invasiveness and metastatic conversion. Our data demonstrate that TH and its modulating enzymes D2 and D3 are critical microenvironmental determinants of tumorigenesis."
But the first paper (about Basal Cell Carcinoma (and hedgehogs, lol) found that applying T3 as a cream directly to the tumor slowed it down .
currently wondering ~ if they know that already, why is no one being offered T3 cream to put on BCC's ? ........since i've conveniently got one on my eyelid to play with , i might try to have an interesting discussion about it with a consultant ... something tells me it will be a more interesting conversation about 'T3 use' than you'd get from an endocrinologist .
"BCC is the most common cancer in humans, and for its treatment, multiple approaches are available, including surgery excision. In some cases, surgery is not a valid option, because tumors may arise close to the eye or on the eyelid. The effect of T3 in reducing tumor growth in a mouse model represents a proof-of-concept of the therapeutic potential use of TH or its analogs in BCCs. Of course, T3 is not devoid of side effects, especially when it is absorbed into the circulation. Studies are required to investigate the possible use of T3-based cream in patients. These findings raise the perspective that TH may have a potential role in the treatment of BCC tumors in humans". (paper published in 2014)
Fascinating Tattybogle. Thing is so little is really known... It's seems like a lot is known but it's not really true as the body is incredibly complex. Amazing really.
The T3 cream sounds an interesting idea. I guess it depends on its strength to how much it would affect the rest of the body and the eye function.. Hope you get it sorted ASAP. I found the cancer specialist a very clever group of professionals with a far more open mind than most. Xx
yes they do seem really good to deal with , so far it's been dealt with hugely better than anything thyroid ever been .... saw dermatology consultant within 7 days of asking GP , was met by 2 of them , they've referred it up to occuloplastic surgeon cos it's too close to the edge of the eyelid for them to handle .
if only i'd known ~ i could have been putting T3 'cream' on this innocuous little bump for years.
Awww love the T3 cream. Surgeons are a different bag and maybe less interested... Lol.
I got shot down in flames by my neurologist because I found an interesting initial piece of research on the effects of B1 injections on Essential Tremor. Unfortunately the chap who did it died from Covid shortly afterwards. Poor man. 7yrs have passed by no one has or is following it up. So I decided to give it a go, B1 being water soluble & simular to b12 in toxicity. I liked the fact the researcher had noted an improvement but especially no further deterioration.. I feel its helping me and given the options out there are pretty rubbish/ ineffective or very drastic, worth a shot... Or two. 🤣😂. Neurologist was positively desirory. Quite took me a back as he's usually a quiet gentle chap. Anyway not to be put off have sent him the research paper!! 😁
Yes that's the paper. It was a very preliminary investigation. It's not proven but I thought it was intriguing. Sadly no big scale research done... Guessing big pharmas not interested and so no money out there to back it. I implemented what he did with some careful checks for contrary indications etc... I didn't have a big improvement but then I take a basic B complex already and I did my jabs subcut not intra muscular. (I'm squeamish!)
It gets very complicated. I don't know of any research that shows low thyroid hormone is of benefit but there are some studies that show higher fT3 or fT4 carries higher risk. I give a summary for breast cancer here ibshypo.com/index.php/thyro... .
There are at least two issues. 1. How do you minimise the risk of cancer overall. and 2. If you have a cancer what is the best thyroid strategy - this is best managed by an oncologist.
There's the added complication that you need to be euthyroid enough to fight the cancer.
It's a complex situation and the research is quite recent. We need to get endcrinologists to acknowledge the risks of monotherapy and then they can work with oncologists if there is a diagnosis.
🤣😂😂👍👍👍 Yes I received lots of training treading that pathway... ... Handy training now! Every cloud has a silver lining! Bet the docs at the time didn't realise what they were creating!! 🤣😂
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