Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

Temozolomide Is Explosive

blogs.sciencemag.org

Post reply on HN
Print view View original

71–80 of 128 posts

Re: Temozolomide Is Explosive

#71

Post by caymanjim »

azinman2 wrote: post #6

Chemotherapy is basically cave man medicine. That a therapeutic drug is explosive only adds to that sentiment. The idea that we'll basically poison you just up to a point that's nearly fatal in order to kill the cancer is such a terrible way to treat someone. Now I'm not saying don't ever do it -- unfortunately that's where we're at in 2021. It's just kind of unbelievable that cancer remains so elusive that we're sti…

Chemotherapy, like cancer, is not one thing. Some of it is a matter of poisoning the body in ways that disrupt rapidly-dividing cells. This is why chemo patients frequently lose their hair (and other things you don't hear as much about, like gametes, fingernails, mucous membranes/digestive lining). You can call this "cave man medicine". Although that's more dismissive than is warranted, there's no denying that it's a blunt instrument.

Other chemotherapy treatments are "holy shit, we live in the future." They're targeted and have almost no side effects.

You specifically reference mustard gas. I had lymphoma, and one of my treatments was bendamustine, which is directly related to that class of chemicals, and the subsequent research. It's broadly toxic. The other treatment was rituximab, which is a monoclonal antibody that targets the CD20 protein that manifests on B cells, which are just one of many cells involved in the lymphatic system.

I have to say the whole thing was a walk in the park. Bendamustine isn't fun, but I never vomited once, never lost my hair, and outwardly didn't look any different at all. I felt pretty shitty for about three days once a month after treatment. Kinda like a mild flu, but honestly I'd take the bendamustine over the flu any day. I usually took three days off work for it, primarily because I had to be at the chemo infusion center for a few hours to get the drugs. I could have worked through it (not that I should ever have had to, but I could have). The rituximab was a walk in the park. I took that once a month for a year, then every two months for two more years. Aside from an allergic reaction the first time (solved with Benadryl subsequently), I barely noticed it at all. It was, at its worst, nowhere near as bad as a hangover.

I know I'm fortunate in that these treatments existed for my cancer, and that my cancer has a high survival rate (I've been clear for over a decade). Many people are far worse off, even if they survive. I like to take these opportunities to dispel some of the misconceptions that are out there.

Re: Temozolomide Is Explosive

#72

Post by aazaa »

The chemical structure is the clue to the explosive potential. The N-N-N triad is a strange beast that shows up in a lot of explosive materials. They're explosive for similar reasons that ammonia nitrate is explosive.

https://www.newscientist.com/article/dn23399-texas-disaster-...

Think of energy as a vertical scale increasing upward. Including a nitrogen triad (like in the drug) pushes the entire molecule up on the energy scale. It's like riding the elevator to the 42nd floor.

In contrast, the N-N triple bond (i.e., atmospheric nitrogen) is way down at the ground floor. This is one reason that despite nitrogen being the most abundant gas in the earth's atmosphere, it requires large amounts of energy to process into fertilizers and other materials.

CO2 and H2O also sit near ground level. So there's a large energy difference between the drug and the combustion products N2, CO2, and H2O.

All it takes to release all of that stored energy is a trigger. For example, if someone were to push you off the top of the building, you would spontaneously release the stored energy. Hopefully you'd be equipped with an air braking device to dissipate it gradually, but if not - well, that energy will be released into your body and the pavement all at once.

Re: Temozolomide Is Explosive

#73

Post by rzzzt »

short_sells_poo wrote: post #69
lmilcin wrote: post #10

I mean, seriously, just look at the molecule. All those nitrogen atoms lying there restless to each go their own separate way:) I would be surprised if it wasn't.

I think some (many) blood vessel dilation meds are based on nitroglycerin :) https://en.wikipedia.org/wiki/Nitroglycerin_(medication) I certainly remember looking with great suspicion at my granddad's medicine and was very much disappointed when my attempts to light his pills on fire did not yield rapid and uncontrolled decomposition.

Wages of Fear, anyone? https://www.imdb.com/title/tt0046268/

Re: Temozolomide Is Explosive

#74

Post by da_chicken »

zaroth wrote: post #58
open-source-ux wrote: post #49

Earlier quoted context omitted.

My understanding is that chemotherapy is indiscrimate when it attacks cells - it affects cancerous and healthy cells alike. However, doctors assume the healthy cells will recover from the weakening effects of chemotherapy. Meanwhile the cancer cells are stressed to a greater degree by the chemotherapy and thus suspectible to death. All this is presented as the "best outcome" scenario for chemotherapy treament. Howeve…

Not entirely indiscriminate. For example as I understand it, a lot of chemo drugs attack cells that divide quickly. Which is why a lot of times hair loss is a side effect because they are some of the faster dividing cells in the body.

My understanding was that chemotherapy drugs often affect cells literally as they divide. The exact mechanisms vary, but it's that timing of affecting a cell during division that makes a given substance possible to be used as chemotherapy drug.

Re: Temozolomide Is Explosive

#75

Post by tyingq »

MisterTea wrote: post #59
tyingq wrote: post #35

Maybe helpful to note that the phrase "Class 1 Explosive" isn't denoting a certain type, or power of "Explosive". "Class 1" in Hazmat is all explosives. Class 2 is Gases. Class 3 is Flammable or Combustible liquid, and so on.

Are you referring to the NFPA diamond? https://en.wikipedia.org/wiki/NFPA_704 The explosive class mentioned is likely using a different scale or standard.

Pretty sure they are talking about Hazmat classes, where "Class 1" is explosives.

See https://www.fmcsa.dot.gov/sites/fmcsa.dot.gov/files/docs/Nin...

Re: Temozolomide Is Explosive

#76

Post by jcims »

Herodotus38 wrote: post #70
et2o wrote: post #60

Earlier quoted context omitted.

Metastatic melanoma? I haven’t seen any data showing close to 50% survival rate, where are you looking? Just managed a young patient with metastatic melanoma and very poor prognosis.

I think they were referring to pd-1 inhibitors. I’m not an oncologist but that generally fits with what I’ve seen as a hospitalist. FWIW I personally know someone who has survived > 5 years who received it right when it cane out. Here’s a paper supporting: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019511/

PD-1 inhibitors seem like magic when they work.

Unfortunately they don’t work in every case, but it’s abundantly clear when they do that the immune system is good at killing unwanted cells roaming around the body. *smacks forehead*

Re: Temozolomide Is Explosive

#77

Post by pcarolan »

azinman2 wrote: post #6

Chemotherapy is basically cave man medicine. That a therapeutic drug is explosive only adds to that sentiment. The idea that we'll basically poison you just up to a point that's nearly fatal in order to kill the cancer is such a terrible way to treat someone. Now I'm not saying don't ever do it -- unfortunately that's where we're at in 2021. It's just kind of unbelievable that cancer remains so elusive that we're sti…

You’re right that we haven’t made much progress but this drug is the only advancement in brain cancer in decades and has very few side effects for most people. Compared to traditional chemotherapy, it is a game changer for many patients’ quality of life.

Re: Temozolomide Is Explosive

#78

Post by dredmorbius »

agumonkey wrote: post #65
dredmorbius wrote: post #39

Earlier quoted context omitted.

A rather surprising number of chemo compounds trace directly to chemical warfare and compounds used during WWI, including several mustard-gas-related compounds. Some years ago, a close friend died of a relatively rare and aggressive form of cancer. Among my roles was running interference against those who were pitching various miracle cures, with that tired old scam laetril playing a significant role. In the decades…

There's a weird wedding here, toxic/warfare compounds dropped into your blood stream and nowadays it's used with administrative processes (for repeatability and liability purposes). Back in the days the people who came with the chemotherapies were also aggressive in the way the approach treatment (and according to De Vita it gave better results [but maybe cost more])

There's also a direct connection to vivisection and human-subjects research during wartime which would fail to meet most ethical review board standards today.

References are pretty easy to find:

After promising animal research, physician researchers connected with Yale University and the University of Chicago tried injecting sulfur mustard and its somewhat milder relatives, the nitrogen mustards, into the veins of cancer patients in the early 1940s. This was the first time a systemic treatment was given for cancer. “It would upset the whole body,” says Smith. “That proved to be valuable when you deal with certain kinds of leukemia or lymphoma.”

https://www.the-scientist.com/foundations/from-chemical-weap...

Not long after the discovery of nitrogen mustard, Sidney Farber of Boston demonstrated that aminopterin, a compound related to the vitamin folic acid, produced remissions in children with acute leukemia.

https://www.cancer.org/cancer/cancer-basics/history-of-cance...

I'm not certain Japan's Unit 731 was engaged in research with chemotherapy precursors, though the range of testing was extensive, and the US provided a grant of immunity after the war.

Please note that pretty much anything horrific you can imagine, and then some, is discussed in the links which follow.

https://nationalinterest.org/blog/reboot/unit-731-japans-sec...

https://en.wikipedia.org/wiki/Unit_731

Re: Temozolomide Is Explosive

#79

Post by robbiep »

et2o wrote: post #60
robbiep wrote: post #15

Earlier quoted context omitted.

The cancers that are treated successfully in children are the blood borne ones (mostly leukemias) and generally because they’re easier to wipe out and replace the marrow with. Some Childhood brain tumours are also very successfully treated, and most other adult cancers children don’t get. Sarcomas still kill people left right and centre though. The truth is that we’re already peeking out of the dark ages of chemother…

Metastatic melanoma? I haven’t seen any data showing close to 50% survival rate, where are you looking? Just managed a young patient with metastatic melanoma and very poor prognosis.

Yes sorry I should have specified, PD-1s. Was 4am in australia on mobile and wasn’t in the mood to reference. Sorry

Re: Temozolomide Is Explosive

#80

Post by cowboysauce »

tyingq wrote: post #42

Found the safety sheet for TMZ: https://www.merck.com/docs/product/safety-data-sheets/hh-sds... Nothing about explosions other than dust explosion warnings, but this one is kind of amusing: "H351 Suspected of causing cancer"

A lot of chemotherapy agents works by causing DNA damage and are therefore carcinogenic themselves.
Post reply on HN