Happy New Year

To all TSZ Members and Readers!

The end of the year and the imminent arrival of the new decade made me wonder when exactly Dr Liddle set this blog up. I see it was in (or at least prior to) August, 2011. Lizzie put up her first opening post Where does information come from? here. You can tell it’s the first because the link is to “hello_world”, the example post that comes with the WordPress package. UD addicts may like to follow this link to exchanges between Lizzie and the charming Upright Biped that may have had some part in the birth of TSZ. So TSZ is well on the way to it’s first decade – a remarkable achievement considering Lizzie has not actively participated here for some years.

Then I mused how much material (over 1,300 opening posts, over a quarter of a million comments) has been buried under the scrolling over. Recently, I was reminded by a Vincent Torley post at Uncommon Descent from 2013 that popped up randomly as a blast-from-the-past of an excellent post here by Allan Miller, Journal club – Protein Space. Big, isn’t it?. Having just re-read it, it seems a shame to me that it lies buried deep in TSZ archives. There is also a follow-up article that is equally meaty (Vincent Torley’s acknowledgement). I then wondered whether some posts and threads here merit a bit of re-exposure. We can bring them to the top of the pile as a featured post for a few days to give an opportunity for further discussion in the light, for example, of further developments.

Does anyone else have a suggestion for a post or a comment that they think deserves more attention than it received first time around?

And wishing everyone a happy and prosperous New Year and decade!

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164 thoughts on “Happy New Year

  1. My wife cut out the Walgreens sign, presumably because of the many pills keeping us alive that we get there.

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  2. J-Mac,
    You go first: what exactly did you say to your ‘client’ with GBM?
    Did you ask her a question about her GBM?

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  3. Allan Miller: Why? I mean, I’m not, but you haven’t really said why either I should or, alternatively, shouldn’t.

    If you not worried about evolution, one way or another, then all both of us can do is follow the argument wherever it leads… In other words, if your altered theory fits the data, I’d be glad to support it. If it happens that it doesn’t, I’d be glad to expose it and you’d be pleased to accept the criticisms not only from Harshman, right?

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  4. DNA_Jock:
    J-Mac,
    You go first: what exactly did you say to your ‘client’ with GBM?
    Did you ask her a question about her GBM?

    I see… So, you already know the lady misunderstood the oncologist, but you don’t want say it, just in case I have someting that would make you look bad as former oncologist? It’s understandable…😉

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  5. walto:
    My wife cut out the Walgreens sign, presumably because of the many pills keeping us alive that we get there.

    👍
    BTW: What’s with men wearing caps everywhere in North America?

    My youngest son was wearing a Boston Bruins cap when we were on the Caribbean vacations last year. A couple from outside of Boston approach us thinking we were from Boston. They were looking for companionship, as people at the resort were rude to them, because they were Americans (due to Trump media nonsense).

    We became friends…thanks to the BB cap….😁

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  6. J-Mac: What if they feel guilt?

    Many of them do, usually as a result of other people disapproving of their sexual orientation. Personally, I can’t of a single valid reason to justify that.

    J-Mac: Who am I to judge? Maybe there is reason (s) we don’t know why?

    Maybe some people project their own sexual morality unto God, in order to justify forcing it upon others? I think you should be perfectly capable of judging other people pretending to know what God approves or disapproves of.

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  7. J-Mac: If you not worried about evolution, one way or another, then all both of us can do is follow the argument wherever it leads… In other words, if your altered theory fits the data, I’d be glad to support it. If it happens that it doesn’t, I’d be glad to expose it and you’d be pleased to accept the criticisms not only from Harshman, right?

    Sure. Though what I predict you’ll say – no matter what I say – is “speculation … lol … Venter … quantum …”, or some such gnomic tosh, because that’s how you appear to ‘do’ science. You have a couple of nails, and you pound them incessantly, and not very clearly. I realise I’m thereby alienating part of my audience before I even start, but I’ll cope.

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  8. J-Mac: I see… So, you already know the lady misunderstood the oncologist, but you don’t want say it, just in case I have someting that would make you look bad as former oncologist? It’s understandable…

    ROFL
    Of course not! What a silly idea. How could I possibly know that she misunderstood the oncologist? All I have to go on is YOUR highly fallible description of your interaction with her. It’s far more likely that the misunderstanding is on your part, not hers. But, to explore that possibility, what exactly did you say to your “client” with GBM?
    and what question did you ask her about her GBM?
    I’ve never been an oncologist.

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  9. phoodoo: You think calling a ban “pre-moderation” isn’t one of Alan’s whims that isn’t in any rule?

    Sorry, premoderation is not a ban unless every premoderated post is never published, is that the case phoodoo?

    If fact many sites use premoderation on new accounts , by you logic those accounts are banned

    But that is not your claim.

    Yes, that was exactly my point. You can claim she was a saint all you want, and Barry can claim she wasn’t following the rules.

    There are no moderation written rules at UD, certainly no guano, no moderation thread , if you want to allow unwritten rules then you undermine your case against Alan.

    Alan is another one of Joe’s saints? Why couldn’t he follow the rules at UD?

    There is are not any rules. Try it, let us know how it goes.

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  10. J-Mac,
    You seem strangely reluctant to answer a couple of straightforward questions:
    what exactly did you say to your “client” with GBM?
    and what question did you ask her about her GBM?
    This way, we can determine whether the misunderstanding was hers, or yours…
    Perhaps we can all benefit from your expertise: does TMZ cause mutations in glial cells, and does TMZ cause mutations in neurons?
    Of course if you “don’t want to say it, just in case I have something that would make you look bad”, I’ll understand.
    We all will.

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  11. Allan Miller: I welcome John’s informed critique. What I don’t welcome is the wilful and persistent ignorance displayed by others hereabouts. John knows what he’s talking about. You, on the evidence before me, not so much. When people don’t trouble to properly understand a subject they presume to critique, a certain testiness is permissible.

    I hope the introduction to your next Evolution of Sex will begin with more humility than this one
    “The Evolution of Sex
    Posted on June 12, 2017 by Allan Miller
    This has long been an interest of mine. It dates back to the old talk.origins days, prompted by a Creationist taunt with familiar tone – “I’d like to see someone explain the evolution of sex …” (with the implicit “hurr, hurr”). I articulated some thoughts, then was rounded on by the ‘mainstream’ community. I got a flavour of the world through Creationist eyes – an equally familiar tone: some very sharply expressed contempt and an invitation to f*** off back to high school and learn meiosis.”

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  12. J-Mac,

    Humility? Not me Guv. Nonetheless, I actually felt I was expressing empathy with Creationists, there, rather than the arrogance you perceive.

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  13. DNA_Jock:
    J-Mac,
    You seem strangely reluctant to answer a couple of straightforward questions:
    what exactly did you say to your “client” with GBM?
    and what question did you ask her about her GBM?
    This way, we can determine whether the misunderstanding was hers, or yours…
    Perhaps we can all benefit from your expertise:does TMZ cause mutations in glial cells, and does TMZ cause mutations in neurons?
    Of course if you “don’t want to say it, just in case I have something that would make you look bad”, I’ll understand.
    We all will.

    What?! You’ve gotta be joking!
    You either have no clue, or didn’t bother to read up on TMZ effects… speaking of looking bad…
    Hint: MMR
    Let me know if you need a link…I😉

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  14. Allan Miller:
    J-Mac,

    Humility? Not me Guv. Nonetheless, I actually felt I was expressing empathy with Creationists, there, rather than the arrogance you perceive.

    By telling them to F-off back to school? I’m sure you have…

    My arrogance? I’m sorry you feel that way…It comes across as such due to the nature of my profession. It’s hard to convince skeptics I found a metabolic pathway responsible for the disorders prevalent in millions of people…
    I try to learn the calm confidence, but it comes across as arrogance sometimes… 😐

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  15. J-Mac: What?! You’ve gotta be joking!
    You either have no clue, or didn’t bother to read up on TMZ effects… speaking of looking bad…
    Hint: MMR
    Let me know if you need a link…I

    Well, you are going to need to be a lot more specific. 😉
    Just to clarify, you appear to be saying that you were discussing the pros and cons of TMZ treatment of GBM with your “client”, and the one question you asked her was about her MMR (mismatch repair) status? Is that correct?

    What exactly did you say to your “client”, and in what “professional” capacity?

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  16. J-Mac: By telling them to F-off back to school? I’m sure you have…

    You’ve misread the passage. People were telling ME to f*** off back to school.

    My arrogance? I’m sorry you feel that way…

    I never even mentioned you. “The arrogance you perceive” was an arrogance perceived by you in me implied by your observation that I lack humility. Perhaps if you read everything twice before responding … ?

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  17. Allan Miller: Perhaps if you read everything twice before responding … ?

    Even reading once would help. J-Mac is in the habit of assuming too much.

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  18. Allan Miller: Indeed. Of the two of us, I’d say the Bible-quoting one is probably the one trying to make things fit preconceived notions. You can’t handle the truth!

    You mean like the preconceived, Bible notion that the universe had a beginning, that has been mocked until recently??? 😉
    Antony Flew came to his senses thanks to this, and other ancient notions… 😉

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  19. J-Mac: You mean like the preconceived, Bible notion that the universe had a beginning, that has been mocked until recently???
    Antony Flew came to his senses thanks to this, and other ancient notions…

    Name-dropping and cherry-picking. Never change, J-mac!

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  20. Allan Miller: You’ve misread the passage. People were telling ME to f*** off back to school.

    My bad! I’m sorry. I guess I’d just found it strange that there would be a lot of obscenities in the creationist literature, or coming out of the church ambons… 🙂

    Allan Miller: I never even mentioned you. “The arrogance you perceive” was an arrogance perceived by you in me implied by your observation that I lack humility. Perhaps if you read everything twice before responding … ?

    It’s probably my short attention span, again… It’s good and bad. It let’s me scan a paper and get just the jest of if. But, in other cases, especially when I drop down my guard, stuff like this happens…

    Anyway, many look forward to your adjusted, sex evolution explanation…
    I have my own wish or suggestion for it too…

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  21. DNA_Jock: Well, you are going to need to be a lot more specific.

    More specific?
    If you believe somatic mutations are the main cause of cancer, why would you recommend a treatment that causes more mutations? There aren’t many pros of the treatment, in my view… Can you see my point?
    Since it turned out you are not an oncologist, and you have not been in the biz since the 90-ties, I assume you didn’t know that TMZ is hypermutogenic in gliomas and possibly beyond… I know you will not admit it…

    DNA_Jock: Just to clarify, you appear to be saying that you were discussing the pros and cons of TMZ treatment of GBM with your “client”, and the one question you asked her was about her MMR (mismatch repair) status? Is that correct?

    What exactly did you say to your “client”, and in what “professional” capacity?

    I have to clarify: my work colleague was recently diagnosed with glioma stage II or III. She had grade II lesions removed-she claims. She is doing radiation. When I visited her, I asked her whether she is going to any preventive/adjunctive treatments. She said no.
    Her work colleague, and best friend, is aware of the preventive/disjunctive therapies (thanks to me) available and probably wouldn’t want her to use TMZ due to hypermutogenic effects…
    Both of them are medical professionals and since I’m not an oncologist, my role is to provide, an opinion, within the scope of my profession… pros and cons, so to speak…

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  22. J-Mac: My bad! I’m sorry. I guess I’d just found it strange that there would be a lot of obscenities in the creationist literature, or coming out of the church ambons…

    Which in itself might have prompted a re-read? 🤣

    There are indeed some massive jerks on both sides. I myself try to be kind and patient, but don’t always succeed.

    It let’s me scan a paper and get just the jest of if.

    Um, if you’re looking for jokes …

    Anyway, many look forward to your adjusted, sex evolution explanation…
    I have my own wish or suggestion for it too…

    It wouldn’t fit … 🤣

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  23. J-Mac,

    Not my area, but I don’t think a treatment being mutagenic should necessarily disbar it. It’s about relative risk. Life is mutagenic. The longer you survive, the more likely cancer is. If mutation rates are elevated, the patient has an increased risk of succumbing to a different cancer in their lifetimes, but if it cures the one they would have died of, that would still be a plus. I’d take it.

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  24. Allan Miller: Which in itself might have prompted a re-read?

    Re-read the post that needs a rewrite?

    Allan Miller: There are indeed some massive jerks on both sides. I myself try to be kind and patient, but don’t always succeed.

    Definitely agreed!

    Allan Miller: Um, if you’re looking for jokes …

    Worked for me! Many people have looked at the same metabolic pathway for years and couldn’t connect the dots… 🙂

    Allan Miller: It wouldn’t fit …

    Try me!

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  25. Allan Miller: Not my area, but I don’t think a treatment being mutagenic should necessarily disbar it. It’s about relative risk. Life is mutagenic. The longer you survive, the more likely cancer is. If mutation rates are elevated, the patient has an increased risk of succumbing to a different cancer in their lifetimes, but if it cures the one they would have died of, that would still be a plus. I’d take it.

    Sure. And patient’s ( we call them clients) have the right to choose and ask for second opinion etc.

    Have you read the paper on TMZ mutational effects on the specific pathways, like MMR?

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  26. J-Mac: Re-read the post that needs a rewrite?

    No, re-read the passage that didn’t ring true. Crikey, it’s like pulling teeth.

    Try me!

    OK, I’ll be round later.

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  27. J-Mac: I have to clarify: my work colleague was recently diagnosed with glioma stage II or III

    Grade III glioma is a high grade glioma and, as per your cited article, is beyond the scope of concern for TMZ-derived mutations. That TMZ contributes to OS is not even in question.

    also as stated in your article (perhaps in your skimming you missed it) is that TMZ treatment in low-grade glioma patients led to significant stability of the tumor enough so that patients were able to delay radiation treatment…..a known contributor to cognitive decline in treated patients. Sounds like you gave some shitty advice to a patient based on your penchant for skimming and missing key points of the research. No surprise there for anyone who has read your post here.

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  28. J-Mac: Have you read the paper on TMZ mutational effects on the specific pathways, like MMR?

    Why yes I have. Why don’t you give it a read, for comprehension this time, instead of giving bogus advice to a patient you aren’t qualified to advise.

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  29. PeterP: Grade III glioma is a high grade glioma and, as per your cited article, is beyond the scope of concern for TMZ-derived mutations.That TMZ contributes to OS is not even in question.

    also as stated in your article (perhaps in your skimming you missed it) is that TMZ treatment in low-grade glioma patients led to significant stability of the tumor enough so that patients were able to delay radiation treatment…..a known contributor to cognitive decline in treated patients.Sounds like you gave some shitty advice to a patient based on your penchant for skimming and missing key points of the research.No surprise there for anyone who has read your post here.

    First,
    Are you familar with DNA _jock and mine conversatons over the last few months???

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  30. PeterP: Why yes I have.Why don’t you give it a read, for comprehension this time, instead of giving bogus advice to a patient you aren’t qualified to advise.

    Second and last:
    I had been asked to provide an opinion. Where did I say I have done it?
    Please re-read the whole thread, though I doubt you can understand anything here…

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  31. Well we have this from you:

    J-Mac: I had been asked to provide an opinion. Where did I say I have done it?

    Sounds like you provided your ignorant insights to someone closely associated with the case.

    J-Mac: Her work colleague, and best friend, is aware of the preventive/disjunctive therapies (thanks to me) available and probably wouldn’t want her to use TMZ due to hypermutogenic effects…

    Patients are free to choose teatment or not. However, receving bogus advice, via you or another, about TMZ hypermutation on a cancer that has already progressed beyond the grade of disease where this might even be a concern is nothing short of criminal, IMO.

    TMZ has the current gold standard of care for glioma(s) is not in question especially for those cancers that are advanced beyond the grade of concern. TMZ’s contributioon to OS and PFS is well documented as is TMZ’s role in treatment of lower grade gliomas to stabilize tumors and delay cognitive-compromising radiation therapy. All this is in the article you cited. If you had bothered to read it you could have presented an informed opinion instead of skimming and missing crucial details that are essential for evaluation of a way forward in treatment of a universally fatal diagnosis of glioma.

    J-Mac: Please re-read the whole thread, though I doubt you can understand anything here

    I understand enough to know that either you did not read the article (highly likely) or that if you did read it you didn’t understand it whatsoever (also highly likely).

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  32. “Int J Cancer. 2019 Jun 15;144(12):3023-3030. doi: 10.1002/ijc.32054. Epub 2019 Jan 7.
    Hypermutagenesis in untreated adult gliomas due to inherited mismatch mutations.
    Sa JK1,2, Choi SW1,3, Zhao J4,5, Lee Y1,2, Zhang J6, Kong DS7, Choi JW7, Seol HJ7, Lee JI7, Iavarone A6,8,9, Rabadan R4,5, Nam DH1,3,7.
    Author information
    Abstract
    Hypermutagenesis refers to marked increase in the number of mutations due to continuous mutagenic process. Hypermutated tumors, have being found in several tumor types, are associated with inherited or acquired alterations in the DNA repair pathways. Hypermutation has been observed in a subset of adult glioma patients as a direct result of temozolomide(TMZ)-induced mutagenesis. In our study, we have identified a rare subset of treatment-naïve adult gliomas with de novo hypermutator phenotype and explored the evolution of spontaneous and treatment-induced hypermutagenesis. We conducted Whole-Exome Sequencing (WES), Whole-Transcriptome Sequencing (WTS), and Single-Cell Sequencing (SCS) of TMZ-naïve and post-TMZ-treated hypermutated tumors to identify distinct clinical or genomic manifestations that contribute to the development of hypermutation in untreated adult gliomas. TMZ-naïve hypermutated tumors were marked by absence of IDH1 somatic mutation and MGMT promoter (pMGMT) methylation, two genomic traits that were significantly associated with the TMZ-induced hypermutagenic event in glioblastoma, and harbored inherited alterations in the mismatch repair (MMR) machinery. The immediate family members of the TMZ-naive hypermutated glioma patients were also previous diagnosed with cancer development history, suggesting that germline dysfunction of the MMR pathway could potentially pose hereditary risk to genetic predisposition of carcinogenesis in gliomas. Lastly, both TMZ-naïve and post-TMZ-treated hypermutated tumors exhibited a significant accumulation of neoantigen loads, suggesting immunotherapeutic alternatives. Our results present new and unique understanding of hypermutagenic process in adult gliomas and an important step towards clinical implication of immunotherapy in glioma treatment.,

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590456/figure/ijc32054-fig-0002/

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  33. J-Mac: More specific?
    If you believe somatic mutations are the main cause of cancer, why would you recommend a treatment that causes more mutations? There aren’t many pros of the treatment, in my view… Can you see my point?

    Yes. That is what I thought you were getting at. And it is exactly as I thought: you don’t understand anything about cancer treatment. Temozolomide, like any other cytotoxic chemotherapy, is mutagen — that’s how it works!
    Safe to say that both of your friends, the medical professionals, would be aware of this. They can probably spell mutAgen correctly, too. Here’s the thing about chemotherapy: it targets rapidly dividing cells — that’s where it is mutagenic. Quiescent cells, like neurons or resting glial cells, not so much. That’s why cytotoxics so often cause anemia, thrombocytopenia, and neutropenia. My questions were designed to give you an opportunity to demonstrate that you understand these things. You failed, miserably.

    Since it turned out you are not an oncologist, and you have not been in the biz since the 90-ties, I assume you didn’t know that TMZ is hypermutogenic in gliomas and possibly beyond… I know you will not admit it…

    Well, you are wrong on all fronts here. Impressive, even by your standards. I have never been an oncologist. My current job does involve me evaluating therapeutic options for many different cancers, including GBM (back in 2017) and discussing these options with KOLs. Unfortunately, the treatment paradigm has not changed since then. There’s a hope that, for patients who are deficient in MMR, the anti-PD(L)-1’s might be effective. Human data is not in yet.

    DNA_Jock: Just to clarify, you appear to be saying that you were discussing the pros and cons of TMZ treatment of GBM with your “client”, and the one question you asked her was about her MMR (mismatch repair) status? Is that correct?

    What exactly did you say to your “client”, and in what “professional” capacity?

    I have to clarify: my work colleague was recently diagnosed with glioma stage II or III. She had grade II lesions removed-she claims. She is doing radiation. When I visited her, I asked her whether she is going to any preventive/adjunctive treatments. She said no.
    Her work colleague, and best friend, is aware of the preventive/disjunctive therapies (thanks to me) available and probably wouldn’t want her to use TMZ due to hypermutogenic effects…
    Both of them are medical professionals and since I’m not an oncologist, my role is to provide, an opinion, within the scope of my profession… pros and cons, so to speak…

    “Adjunctive”? “Disjunctive”? WTF? Did you perhaps mis-hear “adjuvant”?
    I was also giving you every opportunity to show the most basic level of knowledge of the treatment of GBM, something better than “basic J-Mac”. [Basic J-Mac level of thinking: TMZ is a mutagen, MMR repairs mutations, therefore MMR status must be important for the efficacy of TMZ. Sorry, kiddo, but it does not follow.]
    There is a marker that is VERY important is assessing a patient’s prognosis when getting TMZ for their GBM. It is NOT MMR.
    The marker that anyone would ask about when discussing treating GBM, in particular treating GBM with TMZ, is whether the MGMT promoter is methylated. I direct your attention to the NCCN guidlelines version 3.2019, page GLIO-3.
    Given that you have been trying to show that you know what you are talking about, this omission is hilarious.
    You should probably explain what “within the scope of my profession” means — it has got to be an improvement over my current best guess…

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  34. J-Mac: Hypermutated tumors, have being found in several tumor types, are associated with inherited or acquired alterations in the DNA repair pathways

    A study on inherited MMR defects while interesting begs the question of ‘what is the point, jmac’?

    I suspect that this is just another example of you, jmac, not reading the article and instead being a ‘abstract jockey’ desperately searching for anything that says ‘hypermutation’.

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  35. From jmac’s recent citation (not sure what point he was trying to make with it ) but interesting and a positive note for TMZ treatment in patients with inherited MMR disorder(s):

    Our results have shown that spontaneous de novo hypermutated tumors follow an alternative evolutionary trajectory in acquiring continuous mutagenic process via combination of germline and somatic mutations of the mismatch repair genes. Despite having such features, patients with de novo hypermutation exhibited favorable clinical responses to the standard TMZ chemotherapy (Supporting Information Fig. S3), in contrast to the previous notion that inactivation of MSH6 could potentially confer TMZ resistance in glioblastoma.

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  36. DNA_Jock: Yes. That is what I thought you were getting at. And it is exactly as I thought: you don’t understand anything about cancer treatment. Temozolomide, like any other cytotoxic chemotherapy, is mutagen — that’s how it works!
    Safe to say that both of your friends, the medical professionals, would be aware of this. They can probably spell mutAgen correctly, too. Here’s the thing about chemotherapy: it targets rapidly dividing cells — that’s where it is mutagenic. Quiescent cells, like neurons or resting glial cells, not so much. That’s why cytotoxics so often cause anemia, thrombocytopenia, and neutropenia. My questions were designed to give you an opportunity to demonstrate that you understand these things. You failed, miserably.

    Oh Boy! So, we are back were we started few months ago..

    If you believe that cancer is a genetic disease ( vs mine 85% up metabolic disease) caused by mutations and you recommend TMZ that causes more mutations (yes, it can can target cancerous cells by causing mutations in them etc. For example TMZ targets MMR in many cells, which by your own admission has pros and cons, right?

    So, to sum it up, in the end, it is unclear if patients who survive for few months on TMZ and die were killed by gilomas, or by TMZ new mutations, or by poisoning… etc

    But, our conversation started when you recommended keto for gilomas with TZM.

    Since experiments show, TMZ causes vomiting, nausea, lack of appetite and so on… some scientists who do the experiments, like Seyfried, think that similar, or better results, could be accomplished with fasting, ketogenic diet and glucose lowering drugs… WITHOUT SIDE EFFECTS OF TMZ, LIKE POSSIBLY ADDITIONAL MUTATIONS… THAT COULD HAVE THE SAME OR WORSE EFFECT…

    Fasting Enhances the Response of Glioma to Chemo- and Radiotherapy
    Fernando Safdie, Sebastian Brandhorst, […], and Valter D. Longo

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439413/

    Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884883/

    Can you demonstrate, or prove that TMZ treatment is better than keto+fasting+ glutamine blocker? You can’t and that is why you got defensive and failed to answer my challenge in the first place and now…

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  37. PeterP:
    From jmac’s recent citation (not sure what point he was trying to make with it ) but interesting and a positive note for TMZ treatment in patients with inherited MMR disorder(s):

    See my responce to DNA Jock above.
    If you had read our exchange few months ago, you wouldn’t trolling about stuff you don’t understand.
    It boils down to keto+TMZ and mutational affect from TMZ vs keto+fasting no mutational effect from TMZ. Get it? I know you don’t
    Save yourself some time!

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  38. PeterP: A study on inherited MMR defects while interesting begs the question of ‘what is the point, jmac’?

    This is proof you have not read the paper, or as I had suspected earlier, you don’t understand how TMZ affects MMR… The table with drawings of the pathways is in the paper…

    BTW: Look up fasting and autophagy and don’t waste my time!

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  39. DNA_Jock: Safe to say that both of your friends, the medical professionals, would be aware of this. They can probably spell mutAgen correctly,

    I assume you are a PhD, so you don’t know what medical professionals are aware and ar not.
    That’s why the saying goes: ” physician, cure yourself, first” or something
    I’m sorry about the spelling… My new phone self correct is getting used my vocabulary… not that I ever claimed to be the speller of your caliber… lol

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  40. J-Mac: So, to sum it up, in the end, it is unclear if patients who survive for few months on TMZ and die were killed by gilomas, or by TMZ new mutations, or by poisoning… etc

    No, the data is quite clear on this issue reegarding mortality, morbidity, and tolerance of TMZ treatment.

    J-Mac: WITHOUT SIDE EFFECTS OF TMZ, LIKE POSSIBLY ADDITIONAL MUTATIONS… THAT COULD HAVE THE SAME OR WORSE EFFECT…

    Hoo boy…you realize that the studies you are trumpting ALL include treatment with TMZ…..don’t you? Probably not as you show an astounding ignorance of the content of the studies you cite.

    J-Mac: Can you demonstrate, or prove that TMZ treatment is better than keto+fasting+ glutamine blocker? You can’t and that is why you got defensive and failed to answer my challenge in the first place and now…

    Of course anyone can all they have to do is cite the same studies you have provided ALL include TMZ as the SOC treatment NONE show results from a solely alternative approach. You might try reading the studies you cite for comprehension otherwise you come off as quite ignorant of the results of your own citations. The in-vitro study you cited (including the mouse in vivo portion) also contained TMZ as standard treatment.

    All-in-all the only thing you have demonstrated is that TMZ remains the gold standard chemotherapeutic agent for treatment of gliomas. Bottom line you have failed to present a single citation demonstrating that there is any treatment regime for gliomas that do not include TMZ. Nice own goal there!

    J-Mac: This is proof you have not read the paper

    Proof I didn’t read the paper? The inherited MMR defects were outlined right in the title of your citation. How dense can you possibly be….wait…nevermind.

    J-Mac: BTW: Look up fasting and autophagy and don’t waste my time!

    By the way read your own citations for comprehensions and stop wasting everyone’s time as well as soiling the forum with your nonsense.

    J-Mac: It boils down to keto+TMZ and mutational affect from TMZ vs keto+fasting no mutational effect from TMZ. Get it? I know you don’t

    You’ve not presented any data demonstrating that TMZ + keto + anything else leads to zero TMZ mutational effect in gliomas.

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  41. Fingers crossed, should I ever get cancer, I get an oncologist with a predilection for dietary treatments and a short attention span! 🤔

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