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[Sheb]

I hope they fail. Fighting NDM-1 is one of the thing I'm supposed to do for my PhD.

[Sergarr]

I hope they succeed. PhDs are less important than saving people's lives.

[forsaken1111]

Yeah I'll choose life saving advances over your PhD

[ChairmanPoo]

You wont be the first person to get an idea stepped on. I've had several over the years...

Don't worry, you'll get another one if it comes to that.

[Sheb]

He, I was kidding people. :p Interesting though.

[Sheb]

Actually, reading more about that PPMO paper it is quite nice. They use a synthetic oligonucleotide to supress expression of the NDM-1 gene. Does someone has access to the full paper?

Edit: Oh, wait, at first I didn't have access, but now I do get access to the .pdf. Neato.

[PTTG??]

I haven't seen anything about this high ZT stuff since the article came out. At this point I'm starting to suspect that it might be a hoax, since it's so impressive there would have to be some noise about it by now. If accurate, this stuff would be replacing refrigerators.

https://arxiv.org/abs/1612.05344

[wierd]

MoSe2 and MoS2 are not going to be very useful industrially because of the cost of the Molybdenum-- but then again, I suppose the same could be said of neodymium ad osmium, but those are very useful industrially despite the costs...

I dont think there are any industrial scale manufacturing methods for producing this wonder-thermocouple though.

[scrdest]

So today I learned of Opdivo/nivolumab. It's a novel anticancer treatment, very simple in principle - it's just an antibody against a single membrane protein that is hijacked by the cancer cells to eliminate peripheral immune cells that detect something's up.

It works, and it works wide-spectrum, got like eight FDA approvals and breakthrough status, and isn't cytotoxic (it can fuck you up somewhat by inducing autoimmunity, because the protein is normally used for that in lymph nodes against autoreactive Tcs, but y'know, beats LITERAL POISONS), although there's been a recent disappointment in lung cancer where it was no better than chemo. Although probably, y'know, not much worse than, again, literally poisoning yourself for medicine.

Goddamn I am hype.

[ChairmanPoo]

While I commend your enthusiasm for biologicals I resent these statements

Although probably, y'know, not much worse than, again, literally poisoning yourself for medicine.

Don't call chemotherapy "poison". That's what hippy alt-medicine new age healers do  .  No, chemotherapy is not poison. Yes, therapeutical mabs are very interesting, but they don't instantly render other types of treatments pointless. Also, there's a lot of ongoing research in treatments other than biologicals. It's not an either-or-matter. In fact, if you look into the matter, you'll find there's a category called "antibody-drug conjugates" which combine monoclonal antibodies with other types of molecules -eg chemotherapeutical compounds- for enhanced effect.


It's not like mabs don't have side effects, either. In my experience they're annoyingly prone to inducing allergic reactions, and sometimes they cause weird idiosyncratic reactions which have no obvious relation to the mechanism of the drug. 

[forsaken1111]

I mean technically it is poison

1. a substance that is capable of causing the illness or death of a living organism when introduced or absorbed.

[TempAcc]

While I commend your enthusiasm for biologicals I resent these statements

I have no enthusiasm for biologicals, only artificials are deserving of my esteem

[scrdest]

While I commend your enthusiasm for biologicals I resent these statements

Although probably, y'know, not much worse than, again, literally poisoning yourself for medicine.

Don't call chemotherapy "poison". That's what hippy alt-medicine new age healers do  .  No, chemotherapy is not poison. Yes, therapeutical mabs are very interesting, but they don't instantly render other types of treatments pointless. Also, there's a lot of ongoing research in treatments other than biologicals. It's not an either-or-matter. In fact, if you look into the matter, you'll find there's a category called "antibody-drug conjugates" which combine monoclonal antibodies with other types of molecules -eg chemotherapeutical compounds- for enhanced effect.


It's not like mabs don't have side effects, either. In my experience they're annoyingly prone to inducing allergic reactions, and sometimes they cause weird idiosyncratic reactions which have no obvious relation to the mechanism of the drug.

They are literally poisons. The entire mechanism of action of every single cytotoxic therapy is 'hey, this poison will kill the rapidly proliferating cells a bit faster than the rest of the guy'.

It's not 'technically' poison, it's a straight up textbook poison. I've seen cisplatin as a cytotoxicity standard in some papers for crying out loud!  Colchicine and paclitaxel's job is to fuck with tubulins, that's (one of) the mechanisms of methylmercury's toxicity and nobody denies that's toxic.

It's just not a bad thing when you have nothing else. Much in the same way as variolization was deliberately introducing some smallpox into your blood and hoping for the best but was better than straight up praying you won't die of smallpox as the alt-medicine of the times would advise you to.

This thing is cool not because of MAbs themselves; you could probably locate or engineer a small molecule capable of blocking Pd/PdL interactions and it'll work just as well, if not better, it's just that they were easy to engineer as a Thing What Blocks Protein. But the trick here is that you're enabling immune response to work its magic as it's supposed to.

'Course, that means if the immune response is shot for some reason, you won't accomplish much, but we're not burning down the labs and recipes for chemotherapeuticals on launch day either.

[ChairmanPoo]

They are literally poisons. The entire mechanism of action of every single cytotoxic therapy is 'hey, this poison will kill the rapidly proliferating cells a bit faster than the rest of the guy'.

*Everything* is a poison if you go by this rule, because the dose makes the poison.

It's not 'technically' poison, it's a straight up textbook poison. I've seen cisplatin as a cytotoxicity standard in some papers for crying out loud!  Colchicine and paclitaxel's job is to fuck with tubulins, that's (one of) the mechanisms of methylmercury's toxicity and nobody denies that's toxic.

Mabs have a lot of side effects too, just look at the technical file. Not infrequent either: I've seen a lot of people have their bp crash after their first dose of rituximab. And that's without even going into the weird side effects (eg: for some reason there's a surprisingly high amount of people that develop neutropenia two to four months after administering rituximab) or some of the less family-friendly mabs (like alemtuzumab, for instance).

It's just not a bad thing when you have nothing else. Much in the same way as variolization was deliberately introducing some smallpox into your blood and hoping for the best but was better than straight up praying you won't die of smallpox as the alt-medicine of the times would advise you to.

It's not the same at all. Mabs provide additional targets but don't replace or displace chemotherapy because the targets purposes are different. That's why combination therapy is a thing, and indeed, mabs are most often used alongside standard chemotherapy in order to achieve a synergy.

This thing is cool not because of MAbs themselves; you could probably locate or engineer a small molecule capable of blocking Pd/PdL interactions and it'll work just as well, if not better, it's just that they were easy to engineer as a Thing What Blocks Protein. But the trick here is that you're enabling immune response to work its magic as it's supposed to.

And it's real nice, but it's not a magic bullet. That's why you have to help it along. See above.

'Course, that means if the immune response is shot for some reason,

and there are plenty of reasons why this might be a thing in an oncological patient, both treatment related and disease-related.

you won't accomplish much, but we're not burning down the labs and recipes for chemotherapeuticals on launch day either.

You're not burning them at all because it doesn't work like that.

[wierd]

Toxicity is something I think should be looked at based on the LD50 threshold.  If you get an LD50 that is less than 10g, it is definitely a poison, in the traditional sense.  Some poisons are stronger than others, like say, nicotinoids or alkaloids-- while others are very mild, and would require you to eat huge quantities, like say nutmeg.

The deal is, many things that are straight up traditional toxins, are also useful medicinally, because the mechanism by which they cause illness can be therapeutically beneficial in certain circumstances. Cancer is one such application, as is hypertension treatment, and a number of others.