Talk:Tumor necrosis factor

Untitled

I found some historical information here. JFW | T@lk 12:00, 11 December 2005 (UTC)

--- why is it called 'tumor necrosis factor' -- some background would be good, I'll see what I can find --hmackiernan

"Inhibition of TNFα promotes the inflammatory response, which in turn causes many of the clinical problems associated with autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, and psoriasis. These disorders are sometimes treated by inhibiting TNFα "

This seems contradictory. If inhibition of TNFa promotes the inflammatory response, why would you treat these conditions by inhibiting TNFa??

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I noticed the above contradiction as well and think the first part of the phrase must be an error. However, I'm not a medical expert, so I don't dare edit the TNF page.

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I removed the offending phrase (as I am about to refer people to the page). Out of curiosity, I just went back and checked the history. It was clearly an editing glitch, with the phrase left over from what is now covered in the second sentence. -- Bob Kerns

viral replication

doesnt tnf block instead of cause viral replication??? Martious 14:52, 19 January 2007 (UTC)

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How about Tumor Necrosis Factor beta? It is not discussed at all in this page. TNF-alpha is involved in Toxic Shock Syndrome among other things. I can't find any decent (recent) reviews on the topic.

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disabling auto updates

Arcadian, just wondering why you chose to disable all updates of the ProteinBoxBot. Clearly this is a pretty mature article so the impact of PBB edits is proportionally less. (And this was also one of our first edits, and in retrospect, I would not have added the summary and further reading sections where reasonable summaries and reference lists exist.) Was there a particular reason you also wanted to disable the infobox updates? Not trying to convince you otherwise, just trying to understand for the purposes of making sure PBB plays nicely with human editors... AndrewGNF 18:01, 13 November 2007 (UTC)

More general entry: TNF, then subheadings TNF-alpha, TNF-beta?

I'm currently studying this stuff, so I'm no expert, but I'm noticing some confusion. Wouldn't it make sense to merge the entry on TNF with the present one? It could start with a general discussion of TNF and then differentiate between the two types. 85.178.26.162 (talk) 13:30, 6 January 2008 (UTC)

I agree. It is clear to me that this article is much better than the [Tumor necrosis factors]] article (which contains very little). I strongly suggest that they are merged.JustAnotherKinase (talk) 15:29, 4 July 2010 (UTC)

I disagree with the proposed merger because there are (as of 2007) 19 identified members of the TNF family. I agree that this main page is much better than the TNF family ("factors") page, but the family page needs updating and expansion. The expansion would make it unwieldy inside the main TNF page.C4dn (talk) 06:40, 26 July 2011 (UTC)

the first sentence is very good. can you do the same for osteoclast activating factor

osteoclast activating factor has a bunch of different names that it goes by and I think it has sorta evolved with time. I am impressed by the first sentence / alternate names of TNF-alpha and wish someone would do the same for Osteoclast activating factor. Off the top of my head I think it is IL-6 and a subtype of IL-1. But I'm probably wrong so please verify. —Preceding unsigned comment added by 75.43.212.236 (talk) 07:53, 28 April 2008 (UTC)

http://www.google.com/search?q=osteoclast+activating+factor&ie=utf-8&oe=utf-8&aq=t&rls=org.mozilla:en-US:official&client=firefox-a

http://www.grt.kyushu-u.ac.jp/spad/account/ligand/il1.html

http://www.google.com/search?hl=en&safe=off&client=firefox-a&rls=org.mozilla%3Aen-US%3Aofficial&hs=9EO&q=osteoclast+activating+factor+IL-1&btnG=Search —Preceding unsigned comment added by 75.43.212.236 (talk) 07:56, 28 April 2008 (UTC)

Why did  you remove the clooned form in the consept.....  —Preceding unsigned comment added by 85.147.153.152 (talk) 22:56, 14 September 2009 (UTC) 

the cytokine formerly known as

Why does the first sentence include the line "formerly known as tumor necrosis factor-alpha or TNF-α" when it is still currently known as TNF-α? I see that there is a section at the bottom citing a paper which declares the opinion that it should be simply called 'TNF', but this should not imply that everyone else is following this opinion. markwdck (talk) 15:52, 15 February 2013 (UTC)

I totally agree. I the term "TNF" is completely ambiguous, if you read the literature (i.e. pubmed) everyone refers to the cytokine as TNF-α. — Preceding unsigned comment added by 152.23.176.212 (talk) 16:07, 6 March 2013 (UTC)

That's just wrong. "tumor necrosis factor-α" is still being used. E.g. Association between tumor necrosis factor-α antagonists and risk of cancer in patients with inflammatory bowel disease. JAMA. 2014 Jun 18;311(23):2406-13. doi: 10.1001/jama.2014.5613. I'm going to change it. --Nbauman (talk) 05:31, 26 December 2014 (UTC)

Move discussion in progress

There is a move discussion in progress on Talk:Interferon, alpha 1 which affects this page. Please participate on that page and not in this talk page section. Thank you. —RMCD bot 07:59, 15 May 2013 (UTC)

Nomenclature

This article uses TNFα without a hyphen. Elsewhere on wikipedia (such as when discussing TNF-ß), and in some literature, we see it with. Which usage is standard, or can both forms be freely used? --James Chenery (talk) 00:47, 28 June 2018 (UTC)

I see many 2020 journal articles referring to TNF-α, so I see no basis for the claim that this name is obsolete. I have modified this reference in the introduction. --Ben Best:Talk 15:03, 30 December 2020 (UTC)

GA Review

The following discussion is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

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This review is transcluded from Talk:Tumor necrosis factor/GA1. The edit link for this section can be used to add comments to the review.

Nominator: AdeptLearner123 (talk · contribs) 02:00, 1 September 2024 (UTC)

Reviewer: TheNuggeteer (talk · contribs) 01:20, 5 September 2024 (UTC)

From the GARC, going to review this. 🍗TheNuggeteer🍗 01:20, 5 September 2024 (UTC)

Do you still plan on reviewing this? Following up since it's been 7 days. AdeptLearner123 (talk) 00:39, 13 September 2024 (UTC)

IntentionallyDense review

I'm going to help out TheNuggeteer review this article. I'll start by doing a source review. IntentionallyDense (talk) 03:56, 22 September 2024 (UTC)

Good Article review progress box

Criteria: 1a. prose () 1b. MoS () 2a. ref layout () 2b. cites WP:RS () 2c. no WP:OR () 2d. no WP:CV () 3a. broadness () 3b. focus () 4. neutral () 5. stable () 6a. free or tagged images () 6b. pics relevant () Note: this represents where the article stands relative to the Good Article criteria. Criteria marked are unassessed

Source review

• The first thing that jumps out to me here is how old some of your sources are. Per WP:MEDDATE "In many topics, a review that was conducted more than five or so years ago will have been superseded by more up-to-date ones, and editors should try to find those newer sources, to determine whether the expert opinion has changed since the older sources were written." This can be a bit hard to keep up with so I will generally forgive sources written in at least the last 10-20 years however you have sources from the 1940's and that makes me question the reliability of these sources. This is a pretty big topic that I would assume should have more up-to-date sources. I will need to do a full source review to determine if this is a big enough issue to warrant a fail but I would highly encourage you to try to update the sources written before 2000. I do see that some of these are in the history section however there is older sources used in the rest of the article as well. IntentionallyDense (talk) 04:12, 22 September 2024 (UTC)

  I've replaced several pre-2000 references outside of the History section. However, the section Protein > Soluble Form contains information about the secondary / tertiary protein structure that is not included in more recent reviews. Should I keep the old reference or remove this info entirely? AdeptLearner123 (talk) 21:54, 22 September 2024 (UTC)

  Typically if a study or its findings are not referanced in newer studies then they may be outdated and I would kind of go with your best judgement here. WP:MEDDATE says "If recent reviews do not mention an older primary source, the older source is dubious. Conversely, an older primary source that is seminal, replicated, and often-cited may be mentioned in the main text in a context established by reviews" which may be relivant here. IntentionallyDense (talk) 00:11, 23 September 2024 (UTC)

  I feel like the 1989 info about secondary / tertiary is still relevant, as the same paper is referenced in the protein data bank: https://www.rcsb.org/structure/1tnf. My guess for why recent sources have not reviewed this information is because it is not relevant to current areas of research. I feel like we should keep the information and reference the 1989 article, as this is what protein data bank references. AdeptLearner123 (talk) 05:01, 23 September 2024 (UTC)

  That seems reasonable to me as well. IntentionallyDense (talk) 05:26, 23 September 2024 (UTC)

   Done IntentionallyDense (talk) 22:10, 25 September 2024 (UTC)

• I'm seeing a number of references to primary sources as well as animal studies. While the article does make it clear that these are animal studies, this again leads me to question the sources used here. My main question is, does this content need to be here and is there more relevant human studies? While I again recognize that these are mostly used in the history section I am still questioning how relevant these are. IntentionallyDense (talk) 04:12, 22 September 2024 (UTC)

  In the history section, I reference primary sources because I want to describe the experiments that led to a certain discovery. The details of experiments are usually not discussed in review articles, hence I need to cite the primary source. Many of these discoveries, such as the discovery that TNF is a pyrogen, were first discovered in mice, hence the citation of animal studies. AdeptLearner123 (talk) 21:56, 22 September 2024 (UTC)

  That is totally fair and I wrote most of that comment before realizing they were in the history section (oops) however I do feel that the history section itself may be a bit long. I think it might be best to trim some of that section honestly. Even looking at the first paragraph of the history section I might choose to rewrite it from:

  "In the 1890s, William B. Coley, based on anecdotes of cancer patients being cured by sudden attacks of erysipelas, theorized that bacterial infections had a beneficial effect against tumors, particularly sarcomas. Coley was able to successfully treat cancer patients by injecting them with a mixture of bacterial toxins from heat-sterilized Streptococcus and Bacillus prodigiosus in and around the tumors, causing the tumors to hemorrhage. However, the effectiveness of this treatment was inconsistent and repeated injections caused severe side effects such as chills and fevers, causing the treatment to be discontinued"

  to:

  In the 1890s, William B. Coley, based on anecdotes of cancer patients being cured by sudden attacks of erysipelas, theorized that bacterial infections had a beneficial effect against tumors. He successfully treated cancer patients by injecting them with a mixture of bacterial toxins in and around the tumors, causing the tumors to hemorrhage. However, repeated injections caused severe side effects such as chills and fevers, causing the treatment to be discontinued

  I haven't read the source fully so I'm not sure the true weight of the information I removed however little changes like this throughout the history section could be helpful. I will go into more detail about this with the prose review and review of the article but I thought I would give you a heads up about that. IntentionallyDense (talk) 00:19, 23 September 2024 (UTC)

  I personally think that it is important to specify that Coley used these to treat sarcomas, since they are a special type of tumor that is difficult to reach surgically. It also explains why the observation that TNF hemorrhages sarcomas does not generalize to hemorrhaging all tumor types. Otherwise, it may be confusing if the history section says TNF hemorrhages tumors, while the clinical significance section says that TNF promotes tumor growth.

  I also think it is important to mention that the treatment was inconsistent, since it connects to the later observation that endotoxins only hemorrhage tumors in the presence of an infection. Otherwise it would be confusing that Coley's endotoxins killed all sarcomas, while Lloyd's endotoxins did not kill sarcomas.

  On the other hand, I can see how this information is difficult to parse. Maybe I should include additional explanations to make things clearer? That would make the history section even longer though. AdeptLearner123 (talk) 05:06, 23 September 2024 (UTC)

  That is a tricky situation. I have two possible fixes for this.

  1. I would honestly say that you have enough info to split the page from Tumor necrosis factor#History to just History of Tumor necrosis factor and that way you could keep the amount of detail you have in the current article in the History of Tumor necrosis factor (and possibly add some extra extra content to that article cause of the no content forks rule). Then you could summarize what you already have in the history section on the TNF page if that makes sense.
  2. You could try to look through the rest of the history section and see if any of the types of changes I mentioned before could be made to other areas of the article.

  However if you do truly feel that all of the information is relevant then I’m okay with leaving it as is if you aren’t comfortable/don’t want to make a second page for the history section. IntentionallyDense (talk) 05:25, 23 September 2024 (UTC)

  Yeah I feel like the history of TNF is neither long enough nor notable enough to warrant its own page. I'd prefer to keep the content as it is, but if there is any portion that is difficult to understand then I will add additional context. AdeptLearner123 (talk) 05:37, 23 September 2024 (UTC)

  Sounds good I’m happy with that as well however I may ask for a second opinion regarding the readability and length of that section. It depends how I’m feeling with the prose review. I will say that the history section does seem very well worded and fairly easy to follow so good work on that! I will be doing a more in depth source review in the next few days. This includes me manually checking each of your citations for either plagiarism or issues with text source integrity. This might take awhile but I’ll keep you updated as I go! IntentionallyDense (talk) 14:48, 23 September 2024 (UTC)

   Not done With sufficient reasons. IntentionallyDense (talk) 22:11, 25 September 2024 (UTC)

The lead:

• "formerly known as TNF-α, is an inflammatory protein and a principal mediator of the innate immune response."
  Not seeing the part about innate immune response in ref 5, 6, or 7. IntentionallyDense (talk) 22:31, 23 September 2024 (UTC)

  Added citation AdeptLearner123 (talk) 06:04, 24 September 2024 (UTC)

• "It is a member of the tumor necrosis factor superfamily, a family of type II transmembrane proteins that function as cytokines"
  Not seeing the cytokines part in ref 6. IntentionallyDense (talk) 22:31, 23 September 2024 (UTC)

  Changed the reference to a paper that discusses the TNF superfamily and mentions that they are cytokines AdeptLearner123 (talk) 06:02, 24 September 2024 (UTC)

• I'm going to need a page number for ref 11 as the book linked does not have that section. IntentionallyDense (talk) 22:31, 23 September 2024 (UTC)

  This is an online textbook that doesn't have page numbers. I referenced section 11.3C which is only a single page long. It can be found at this url https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Kaiser)/Unit_5%3A_Innate_Immunity/11.4%3A_Early_Induced_Innate_Immunity/11.3C%3A_Cytokines_Important_in_Innate_Immunity AdeptLearner123 (talk) 05:49, 24 September 2024 (UTC)

  Is there any way you could add that URL to the citation? IntentionallyDense (talk) 18:25, 24 September 2024 (UTC)

  Done AdeptLearner123 (talk) 23:49, 25 September 2024 (UTC)

• Otherwise I was able to verify all other sources. No plagiarism issues. IntentionallyDense (talk) 22:31, 23 September 2024 (UTC)

 Done IntentionallyDense (talk) 03:09, 28 September 2024 (UTC)

History:

• The link/PMCID in ref 15 links to [1] while the doi and PMID link to [2]. Please clarify which article you are meaning to use here. IntentionallyDense (talk) 21:45, 25 September 2024 (UTC)
• Aside from the first paragraph the Discovery section is all verifiable and there are no plagiarism issues. IntentionallyDense (talk) 21:45, 25 September 2024 (UTC)
• Isolation, sequencing, and expression all verified and no plagiarism. IntentionallyDense (talk) 21:56, 25 September 2024 (UTC)
• Rest of the history section is verified. No plagiarism issues found. IntentionallyDense (talk) 22:09, 25 September 2024 (UTC)

Fixed the PMCID for ref 15. AdeptLearner123 (talk) 23:53, 25 September 2024 (UTC)

 Done IntentionallyDense (talk) IntentionallyDense (talk) 03:09, 28 September 2024 (UTC)

Protein:

• "Both tmTNF and sTNF are bioactive and assembled as homotrimers" not seeing this part in the source. IntentionallyDense (talk) 19:53, 27 September 2024 (UTC)
• Otherwise verified and no plagiarism. IntentionallyDense (talk) 19:53, 27 September 2024 (UTC)

Updated the reference AdeptLearner123 (talk) 18:53, 28 September 2024 (UTC)

 Done IntentionallyDense (talk) 22:41, 30 September 2024 (UTC)

Function:

• "TNF is a central mediator of the body's innate immune response." not verified by ref 6. IntentionallyDense (talk) 19:53, 27 September 2024 (UTC)
• Otherwise verified with no plagiarism. IntentionallyDense (talk) 19:53, 27 September 2024 (UTC)

  Updated reference AdeptLearner123 (talk) 18:58, 28 September 2024 (UTC)

 Done IntentionallyDense (talk) 22:41, 30 September 2024 (UTC)

The rest:

• I did some spot-checks for the rest of the article and they came back clean. This combined with how few issues I found with sources makes me believe this article is well-sourced. IntentionallyDense (talk) 20:00, 27 September 2024 (UTC)

• I missed this before but under expression the following statement is unsourced: "The TNF gene is also an immediate early response gene; its activation is rapid and does not depend on the synthesis of other proteins." I added a cn tag to help you find it. IntentionallyDense (talk) 03:15, 28 September 2024 (UTC)

  Updated reference AdeptLearner123 (talk) 19:01, 28 September 2024 (UTC)

 Done IntentionallyDense (talk) 22:42, 30 September 2024 (UTC)

Prose review

• Before getting too much into the source review I want to voice my concerns about readability with this article. I understand how hard it can be to make these kinds of articles easy to understand however this is a part of the GA criteria. The lead (particularly the first 3 paragraphs) need to be made more understandable to a broad audience. The history section I think needs to be trimmed a bit. The section "Isolation, sequencing, and expression" could use some work to make it more readable as well. The gene and protein sections could also use some modifications to make them more readable. Wikipedia:Make technical articles understandable is a great place to start with tackling this type of thing. IntentionallyDense (talk) 04:17, 23 September 2024 (UTC)
• The first time you use an acronym it needs to be used in full per MOS:1STOCC. There are many occasions in this article where you use acronyms without putting the full form. If you could fix this that would be helpful. IntentionallyDense (talk) 20:00, 27 September 2024 (UTC)

  The acronyms seem to be in the following categories:

  • Names of techniques: DEAE, HPLC, SDS-PAGE
  • Commonly known acronyms: cDNA, mRNA
  • Protein names: TNFR1, TNFR2, GM-CSF, NFAT, ATF-2, Ets, etc

  I've expanded TNFR1 / TNFR2 to the full form in the first occurrence. I'm not sure how helpful it would be to use the full forms of acronyms that are names of techniques or proteins, since they aren't that descriptive of their function. What do you think? AdeptLearner123 (talk) 19:10, 28 September 2024 (UTC)

  I think the gene names are okay for sure as well as the common acronyms however i do remember reading something in the history section about sequencing that had an acronym not previously defined. i’m on mobile right now but i’ll come back to this when on my laptop. IntentionallyDense (talk) 22:04, 28 September 2024 (UTC)

• The lead needs to be made less technical but I think the other sections are okay. IntentionallyDense (talk) 03:08, 28 September 2024 (UTC)

  Can you point me to the sentences that are too technical? I'll try to reword and add context to make it less technical, although I'm hesitant to remove information as I feel like each sentence is important for an overview. AdeptLearner123 (talk) 19:18, 28 September 2024 (UTC)

  I understand it’s difficult to make things less technical but a lot of people just read the lead. I’m on my phone right now but tomorrow I will break down each sentence of the lead and point out which ones are in my opinion too technical. information doesn’t necessarily need to be removed just made more understandable. sometimes this does involve removing info but you could always add some of that info back into the body of the article. IntentionallyDense (talk) 22:09, 28 September 2024 (UTC)

  As promised I am going to copy and paste the entire lead and colour code it. green means it is understandable, yellow means I'm unsure, and red means it is too technical.

  Tumor necrosis factor (TNF), formerly known as TNF-α, is an inflammatory protein and a principal mediator of the innate immune response. TNF is produced primarily by macrophages in response to antigens, and activates inflammatory pathways through its two receptors, tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2 (TNFR2). It is a member of the tumor necrosis factor superfamily, a family of type II transmembrane proteins that function as cytokines. Excess production of TNF plays a critical role in the pathology of several inflammatory diseases, and anti-TNF therapies are often employed to treat these diseases.

  TNF is expressed primarily by macrophages but is also expressed in several other cell types, such as T cells, B cells, dendritic cells, and mast cells. It is expressed in response to pathogens, other cytokines, and environmental stressors. TNF is initially produced as a type II transmembrane protein (tmTNF) and assembled as a homotrimer, which is then cleaved by TNF alpha converting enzyme (TACE) into a soluble form (sTNF), allowing it to be secreted into the extracellular space. Both tmTNF and sTNF can activate TNFR1, while only tmTNF can activate TNFR2.

  TNFR1 can trigger inflammatory pathways, producing effects such as cell survival and proliferation, as well as cell death if the inflammatory pathways are disrupted. TNFR2 can only trigger cell survival and proliferation, but can indirectly induce cell death by disrupting TNFR1. tmTNF also sends reverse signals into its own cell, leading to cell death or survival depending on circumstances. TNF's effects on the immune system include the activation of white blood cells, blood coagulation, secretion of cytokines, and fever, among others. The activity of TNF extends beyond the immune system, such as contributing to homeostasis in the central nervous system.

  The excessive production of TNF is known to be a key factor in inflammatory disorders such as rheumatoid arthritis and inflammatory bowel disease, and the inhibition of TNF is often an effective treatment. TNF is also implicated in the pathology of other diseases including cancer, liver fibrosis, and Alzheimer's, although TNF inhibition has yet to show definitive benefits. Due to the important role of TNF in innate immunity and homeostasis, the inhibition of TNF can lead to increased risk of infections and new "paradoxical" autoimmunities.

  I would focus on the red setences first. most of the yellow ones just have a couple of words that are hard to understand. I'll further break down some of the issues with the yellow setences but in green cause yellow is hard to read.

  Tumor necrosis factor (TNF), formerly known as TNF-α, is an inflammatory protein and a principal mediator of the innate immune response. Some readers might be confused by what "inflammatory protein" means in this context. Not a huge deal but could be made more readable.

  Excess production of TNF plays a critical role in the pathology of several inflammatory diseases, and anti-TNF therapies are often employed to treat these diseases. I would define what "anti-TNF therapies" are.

  TNF is expressed primarily by macrophages but is also expressed in several other cell types, such as T cells, B cells, dendritic cells, and mast cells. It might be helpful to explain what you mean by "expressed by".

  I do have to go right now but I will continue to break down the setences I highlighted if it is helpful for you. IntentionallyDense (talk) 18:52, 29 September 2024 (UTC)

  Thanks, the breakdowns are quite helpful and I will work on them soon. Could you also give me a breakdown of the four red sentences? I'm not sure which terms are too technical in these sentences. AdeptLearner123 (talk) 22:38, 29 September 2024 (UTC)

  I'll continue to breakdown what I can.

  TNF is produced primarily by macrophages in response to antigens, and activates inflammatory pathways through its two receptors, tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2 (TNFR2). It is a member of the tumor necrosis factor superfamily, a family of type II transmembrane proteins that function as cytokines There is just a lot of technical terms here and I'm not sure if you're able to simplify these.

  TNF is initially produced as a type II transmembrane protein (tmTNF) and assembled as a homotrimer, which is then cleaved by TNF alpha converting enzyme (TACE) into a soluble form (sTNF), allowing it to be secreted into the extracellular space. Again a lot of technical terms I'm not sure if there is any way to make this less technical but it's not very understandable to a broad audience.

  TNFR1 can trigger inflammatory pathways, producing effects such as cell survival and proliferation, as well as cell death if the inflammatory pathways are disrupted. TNFR2 can only trigger cell survival and proliferation, but can indirectly induce cell death by disrupting TNFR1. maybe explain what you mean by inflammatory pathways.

  tmTNF also sends reverse signals into its own cell, leading to cell death or survival depending on circumstances. Explain what reverse signals are and what circumstances are involved.

  The excessive production of TNF is known to be a key factor in inflammatory disorders such as rheumatoid arthritis and inflammatory bowel disease, and the inhibition of TNF is often an effective treatment. Same as the other comment about TNF in regards to the treatment of other disorders.

  Due to the important role of TNF in innate immunity and homeostasis, the inhibition of TNF can lead to increased risk of infections and new "paradoxical" autoimmunities. What do you mean by inhibition and new "paradoxical" autoimmunities? IntentionallyDense (talk) 22:25, 30 September 2024 (UTC)

  I have rewritten the lead with simpler language. Please let me know if it is still unaccessible. I will also try to make some of the other sections more accessible too. AdeptLearner123 (talk) 06:27, 2 October 2024 (UTC)

• "cancer patients" I would change this to "people with cancer" per WP:MEDLANG. IntentionallyDense (talk) 03:08, 28 September 2024 (UTC)

  I used "cancer patients" in the History section since that was their relation to William Coley, who was a surgeon and cancer researcher. I'm also concerned that using "people with cancer" will make the sentence more convoluted. AdeptLearner123 (talk) 19:20, 28 September 2024 (UTC)

  I think it’s okay since you’re talking about a case study so I won’t fight you on this one but it’s something to watch out for with the rest of the article. IntentionallyDense (talk) 22:06, 28 September 2024 (UTC)

   Not done With reasoning. IntentionallyDense (talk) 23:45, 30 September 2024 (UTC)

• "Coley was able to successfully treat cancer patients by injecting them with a mixture of bacterial toxins from heat-sterilized Streptococcus and Bacillus prodigiosus in and around the tumors, causing the tumors to hemorrhage" bit of a run-on sentence. IntentionallyDense (talk) 03:08, 28 September 2024 (UTC)

  ignore this it’s not a run on just long. IntentionallyDense (talk) 22:10, 28 September 2024 (UTC)

• "In addition to causing sarcomas to hemorrhage in vivo, TNF was also cytotoxic to L-929 cells, a transformed cell line, in vitro. Cytotoxicity to L-929 cells in vitro became the standard technique for detecting TNF. TNF was cytotoxic to cancerous and transformed cell lines, but not to normal, untransformed cell lines, raising hopes that it could be used as a cancer therapy." I think it's important to define what in vivo and in vitro mean in this context as I'm a bit confused by this statement. IntentionallyDense (talk) 03:08, 28 September 2024 (UTC)

  Added definitions. I reworded the paragraph a bit to hopefully make it more accessible to a wider audience. I'm wondering if "neoplastic cell line" is too technical, and if I should use "abnormal cell line" instead. "Abnormal" is a bit vague, but easier to understand. What do you think? AdeptLearner123 (talk) 05:31, 29 September 2024 (UTC)

  I think the setence looks much better now and neoplastic cell line should be okay. IntentionallyDense (talk) 18:39, 29 September 2024 (UTC)

   Done IntentionallyDense (talk) 23:46, 30 September 2024 (UTC)

• "The observation that TNF induces wasting and endotoxic shock led to rethinking its potential role as a cancer therapy." This is a bit vague, could you expand on this? IntentionallyDense (talk) 03:08, 28 September 2024 (UTC)

  I reworded this to "The adverse side effects of TNF, such as muscle wasting and endotoxin shock, reduced hopes that it could be used to treat cancer." This makes it clearer what "rethinking" is referring to. Lmk if any other part is vague AdeptLearner123 (talk) 05:40, 29 September 2024 (UTC)

  That sounds good. IntentionallyDense (talk) 18:39, 29 September 2024 (UTC)

   Done IntentionallyDense (talk) 23:46, 30 September 2024 (UTC)

• There is a couple times where I feel like your sentences kinda jump all over the place. for example the sentence "In the 1890s, William B. Coley, based on anecdotes of cancer patients being cured by sudden attacks of erysipelas, theorized that bacterial infections had a beneficial effect against tumors, particularly sarcomas." jumps back and forth when it could be reworded to In the 1890s, William B. Coley theorized that bacterial infections had a beneficial effect against tumors, particularly sarcomas, based on anecdotes of cancer patients being cured by sudden attacks of erysipelas. The second sentence flows much better. Some other examples of this include {alternating colours so you can tell when one sentence ends and another begins): They discovered that mice infected with Bacillus Calmette Guerin (BCG), upon exposure to endotoxin, produced serum that could kill sarcomas in other mice. Meanwhile, uninfected mice, upon exposure to endotoxin, produced serum that did not kill tumors. In June 1981, Ian A. Clark et al. found that healthy mice infected with Plasmodium vinckei, a malaria-causing parasite, upon exposure to endotoxin, developed malaria-like symptoms such as liver damage, hypoglycemia, and blood clotting, while also releasing mediators including TNF. and In September 1981, Masanobu Kawakami and Anthony Cerami investigated the tendency of endotoxins to cause high levels of fat in the blood, known as hypertriglyceridemia, when injected into animals. These 5 examples are just from the history section alone. I would advise you to check over the rest of the article to see if this is a reoccurring issue. IntentionallyDense (talk) 03:08, 28 September 2024 (UTC)

  I reworded the first four sentences. I'm not sure how I can reword the last sentence to be more clear. The rest of the article seems to have more straightforward sentences, but let me know if you see anything else that needs to be simplified. AdeptLearner123 (talk) 06:45, 29 September 2024 (UTC)

  Sounds good. The last setence is a bit harder to reword and I was moreso asking if there was a better way to word it. IntentionallyDense (talk) 18:40, 29 September 2024 (UTC)

   Done IntentionallyDense (talk) 23:46, 30 September 2024 (UTC)

• reduced hopes that it could be used to treat cancer The use of the word "hopes" seems odd here. IntentionallyDense (talk) 22:40, 30 September 2024 (UTC)

  Reworded AdeptLearner123 (talk) 19:03, 2 October 2024 (UTC)

• Just reading through the "Gene" section and it seems like there are a couple of random sentences that could be combined into another paragraph. For example The flexibility of the enhanceosome enables the TNF gene to be activated by a wide range of cell types and stimuli. Is separated on its own and that kinda looks awkward. There are quite a few other examples of this throughout the article. Is it possible for you to fix this? IntentionallyDense (talk) 22:40, 30 September 2024 (UTC)

  I've fixed all instances of this, except for the Central Nervous System section AdeptLearner123 (talk) 07:51, 4 October 2024 (UTC)

• As I read through the protein and gene section I'm noticing quite a few words which could be wikilinked but aren't. I'll try to fix those myself but it's something to look out for. IntentionallyDense (talk) 23:23, 30 September 2024 (UTC)

  Sounds good, I've fixed a few. Lmk if you see any more AdeptLearner123 (talk) 07:51, 4 October 2024 (UTC)

• I've mostly avoided suggesting adding extra explanations for this article as I do understand it's meant to be written for a higher education level however I do feel it would be valuable to give a bit more of a description of the innate immune system somewhere in this article. The reason I say this is because it is super important to the topic and I feel like adding a quick explanation, possibly to the paragraph The innate immune system is activated when pathogen-associated molecular patterns (PAMPs), such as endotoxins and double-stranded viral RNA, bind to the pattern recognition receptors (PRRs) of immune cells, causing them to secrete immune-regulating cytokines. These cytokines, such as IL-1, IL-6, IL-8, and TNF, are primarily secreted by mononuclear phagocytes, such as macrophages and dendritic cells. They mainly act on white blood cells, also known as leukocytes, as well as on endothelial cells in blood vessels to promote an early inflammatory response. would fit in nicely and help readers. IntentionallyDense (talk) 23:28, 30 September 2024 (UTC)

  Added AdeptLearner123 (talk) 08:00, 4 October 2024 (UTC)

• I'm wondering if the section "Taste perception" might belong under "Clinical significance" just as it discusses the role of TNF in anorexia. I can see an argument for it belonging to either section but I'm curious about what you think. IntentionallyDense (talk) 23:31, 30 September 2024 (UTC)

  Fair point, I will move it to Clinical Significance AdeptLearner123 (talk) 19:05, 2 October 2024 (UTC)

• In the section "Clinical significance" you talk about TNF blockers quite a bit in an almost repetitive manner. For example under the "Autoimmunity" you state TNF blockers are used to treat these diseases, often with high efficacy. and then in the next paragraph say Drugs that target specifically the cell death pathway of TNF are being evaluated for their efficacy against autoinflammatory diseases. These two sentences seem to be saying relatively the same thing. Throughout the rest of the section you talk about the role of TNF in medical treatments. I would just be careful about repeating similar information. IntentionallyDense (talk) 23:35, 30 September 2024 (UTC)

  These two sentences are saying different things. The first sentence refers to drugs that prevent TNF from binding to its receptors. The second sentence refers to drugs that disrupt the cell signaling pathway after TNF has bound to the target cell. I have reworded these sentences to make it more clear. AdeptLearner123 (talk) 08:02, 4 October 2024 (UTC)

• TNF plays a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). When fat builds up in the liver, termed steatosis, hepatocytes, Kupffer cells, and infiltrating immune cells secrete TNF. I'm a little unsure of what you are trying to say with the second sentence. I assume you are explaining what NAFLD is but your current wording isn't super clear with that. IntentionallyDense (talk) 23:39, 30 September 2024 (UTC)

  I have reworded this section to make things simpler and clearer AdeptLearner123 (talk) 08:56, 4 October 2024 (UTC)

Image review

• All the images besides the infobox image were uploaded by you. They all say own work. I do not want to come across as accusatory but these graphics are very good quality and I just want to confirm that these are indeed your own work. IntentionallyDense (talk) 22:04, 25 September 2024 (UTC)

  Thanks! The diagram renders were made on my own using Powerpoint, the protein models were made on my own using PyMol. AdeptLearner123 (talk) 23:22, 25 September 2024 (UTC)

  Very impressive, I hope you will consider uploading more images in the future! IntentionallyDense (talk) 03:10, 28 September 2024 (UTC)

Final comments

• I'm going to place this on hold until the prose issues are addressed. Overall this is a really impressive article. I'm impressed by the nominator's knowledge on the topic and I'm happy to have been apart of this review! IntentionallyDense (talk) 23:42, 30 September 2024 (UTC)

  I've rewritten the lead, can you verify if it is accessible enough? AdeptLearner123 (talk) 06:28, 2 October 2024 (UTC)

  I think I'm going to ask for a second opinion here cause I'm having a hard time tackling this page on my own. I'm sorry for the wait. IntentionallyDense (talk) 14:45, 2 October 2024 (UTC)

  Came here from your post at WT:MED. I think the lead looks good, and would be understandable by an appropriately broad audience (this is a topic that is probably introduced to latter-half university students majoring in a molecular biology-like field? So I'm reading the lead with the introductory molecular biology student in mind, per the rule of thumb WP:ONEDOWN). If there's more you'd like a second opinion on, let me know and I'm happy to opine. Ajpolino (talk) 20:01, 3 October 2024 (UTC)

  Thank you for weighing in on the topic. While I do agree with what you said I was kind of told that the lead should be even more introductionary than the body. Would you say that the lead is appropriately technical? Obviously I'm not saying it needs to be at a grade 6 reading level but it should be somewhat understandable to someone just browsing Wikipedia. IntentionallyDense (talk) 20:53, 3 October 2024 (UTC)

  The guideline leaves a large gray area in which reasonable people can disagree. I think the lead is appropriately accessible to meet the relevant GA criterion (haven't assessed the rest of the article). Either way, it's ultimately up to you as the GA reviewer. Ajpolino (talk) 18:49, 4 October 2024 (UTC)

  Thank you. Your input is very much appreciated! IntentionallyDense (talk) 22:14, 6 October 2024 (UTC)

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.