Support the Arctic Sea Ice Forum and Blog

Author Topic: An Omega-3 That’s Poison for Cancer Tumors  (Read 5388 times)

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
An Omega-3 That’s Poison for Cancer Tumors
« on: June 14, 2021, 07:33:03 PM »
hope this holds up, is a simple function.

The poison acts on tumor cells via a phenomenon called ferroptosis, a type of cell death linked to the peroxidation of certain fatty acids. The greater the amount of unsaturated fatty acids in the cell, the greater the risk of their oxidation. Normally, in the acidic compartment within tumors, cells store these fatty acids in lipid droplets, a kind of bundle in which fatty acids are protected from oxidation. But in the presence of a large amount of DHA, the tumor cell is overwhelmed and cannot store the DHA, which oxidizes and leads to cell death. By using a lipid metabolism inhibitor that prevents the formation of lipid droplets, researchers were able to observe that this phenomenon is further amplified, which confirms the identified mechanism and opens the door to combined treatment possibilities.

For their study, UCLouvain researchers used a 3D tumor cell culture system, called spheroids. In the presence of DHA, spheroids first grow and then implode. The team also administered a DHA-enriched diet to mice with tumors. The result: tumor development was significantly slowed compared to that in mice on a conventional diet.

This UCLouvain study shows the value of DHA in fighting cancer. “For an adult,” the UCLouvain researchers stated, “it’s recommended to consume at least 250 mg of DHA per day. But studies show that our diet provides on average only 50 to 100 mg per day. This is well below the minimum recommended intake.”

https://scitechdaily.com/an-omega-3-thats-poison-for-cancer-tumors/

Reference: 11 June 2021, Cell Metabolism.
DOI: 10.1016/j.cmet.2021.05.016

Jim Hunt

  • First-year ice
  • Posts: 6330
  • Don't Vote NatC or PopCon, Save Lives!
    • View Profile
    • The Arctic sea ice Great White Con
  • Liked: 906
  • Likes Given: 87
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #1 on: June 14, 2021, 09:03:09 PM »
So just eat lots of fish?

Where to get at least 250 mg of DHA per day in your food if you're vegan/vegetarian?
"The most revolutionary thing one can do always is to proclaim loudly what is happening" - Rosa Luxemburg

SteveMDFP

  • Young ice
  • Posts: 2599
    • View Profile
  • Liked: 613
  • Likes Given: 49
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #2 on: June 14, 2021, 11:01:16 PM »
So just eat lots of fish?

Where to get at least 250 mg of DHA per day in your food if you're vegan/vegetarian?

Hard to find, but algae oil.  Fish don't make their own DHA, they get it in the food chain.
If you don't mind eating tiny animals, krill oil would also do the trick.  That's more widely available.

If fish knew how healthy their flesh was for humans, I'm sure fish would volunteer to be eaten.

WildFit

  • Grease ice
  • Posts: 515
    • View Profile
  • Liked: 110
  • Likes Given: 79
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #3 on: June 15, 2021, 12:43:37 AM »
So just eat lots of fish?

Where to get at least 250 mg of DHA per day in your food if you're vegan/vegetarian?

Nuts for one, wanna know more google is your friend but there are plenty of non-cadaverous sources.  :) :) :) :) :)


Of course you mostly have to scroll down a bit because fish and such are  usually on top.

ivica

  • Nilas ice
  • Posts: 1507
  • Kelele
    • View Profile
  • Liked: 100
  • Likes Given: 0
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #4 on: June 15, 2021, 12:03:13 PM »
This do not answers Jim's question, anyway - blog: Plant-Based Omega-3: What is ALA? | Fullscript

Quote
How to get omega-3 as a vegan or vegetarian
You can find omega-3 in land-based plants containing ALA or sea-based plants that contain EPA and DHA, but the latter must be consumed as extracts in supplemental format. (7) Examples of ALA-containing whole foods include flaxseeds and walnuts. (2) When ALA is consumed, it’s converted by enzymes in our bodies into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

i have to eat so i eat what i have :), like purslane - showing up these days everywhere in garden, even in pots...


nukefix

  • Grease ice
  • Posts: 546
    • View Profile
  • Liked: 27
  • Likes Given: 9
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #5 on: June 15, 2021, 03:51:48 PM »
ALA won't cut it but as mentioned EPA&DHA are available from vegan sources.

SteveMDFP

  • Young ice
  • Posts: 2599
    • View Profile
  • Liked: 613
  • Likes Given: 49
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #6 on: June 15, 2021, 07:45:53 PM »
ALA won't cut it but as mentioned EPA&DHA are available from vegan sources.

Exactly.  Sources such as nuts, flax, and safflower oil may contain abundant ALA, but negligible EPA or DHA.  DHA was the original fatty acid under discussion.  The body can convert some ALA to DHA, but to a very limited extent.  See;

Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)?
https://pubmed.ncbi.nlm.nih.gov/9637947/

"The parent fatty acid ALA (18:3n-3), found in vegetable oils such as flaxseed or rapeseed oil, is used by the human organism partly as a source of energy, partly as a precursor of the metabolites, but the degree of conversion appears to be unreliable and restricted. More specifically, most studies in humans have shown that whereas a certain, though restricted, conversion of high doses of ALA to EPA occurs, conversion to DHA is severely restricted. The use of ALA labelled with radioisotopes suggested that with a background diet high in saturated fat conversion to long-chain metabolites is approximately 6% for EPA and 3.8% for DHA. With a diet rich in n-6 PUFA, conversion is reduced by 40 to 50%."


So it really is fish oil for pescatarians, algae oil for vegans.

WildFit

  • Grease ice
  • Posts: 515
    • View Profile
  • Liked: 110
  • Likes Given: 79
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #7 on: June 15, 2021, 10:23:58 PM »


So it really is fish oil for pescatarians, algae oil for vegans.


While thanking for the detailed explanations that are one of the best ever read in a few lines, one question as to the "Oils"

Why are oils that much promoted? I usually recommend to have the original, means olives instead of olive oil if possible, fish instad of fish oil and algea instead of algae oil. The original sources of any oil IMO have huge benefits themselves and then the energy to volume relation is somehow better for people who tend to eat greater volumes of food.

What do you think?

SteveMDFP

  • Young ice
  • Posts: 2599
    • View Profile
  • Liked: 613
  • Likes Given: 49
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #8 on: June 15, 2021, 10:51:18 PM »
So it really is fish oil for pescatarians, algae oil for vegans.

While thanking for the detailed explanations that are one of the best ever read in a few lines, one question as to the "Oils"

Why are oils that much promoted? I usually recommend to have the original, means olives instead of olive oil if possible, fish instad of fish oil and algea instead of algae oil. The original sources of any oil IMO have huge benefits themselves and then the energy to volume relation is somehow better for people who tend to eat greater volumes of food.

What do you think?

Well, yes.  It's probably better to get these oils from actual food rather than supplements.  American Heart Association recommends eating fish for cardiac health, not supplements.  I believe the observational evidence is stronger for fish than for supplements.

This was more clearly seen with e.g. beta-carotene and cancer.  People with diets high in beta carotene were noted to have lower rates of cancer.  Under experimental protocols, however, beta carotene supplements did not decrease cancer rates.  See, for example:

Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: A Randomized Controlled Trial
https://academic.oup.com/jnci/article/101/1/14/914826?login=true

There are a lot more components to real food than just a supplement or two will contain.  This reminds me to put more salmon and sardines on my shopping list.  And holy mackerel !

be cause

  • Young ice
  • Posts: 2506
    • View Profile
  • Liked: 1039
  • Likes Given: 1099
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #9 on: June 16, 2021, 12:46:37 AM »
LOL .. just in from packing the sardines for a mini-holiday with mother (93); after enjoying salmon for lunch and kippers for tea . Holy mackerel will have to wait 'till we get to Bunagee . :)
There is no death , the Son of God is We .

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #10 on: June 20, 2021, 09:54:48 PM »
good analysis folks, thanks.

Also, do not take beta carotene if you are a smoker. They had to stop a study on using for heart and cancer, and had to halt the study cause all the smokers started dieing.

Rodius

  • Nilas ice
  • Posts: 2289
    • View Profile
  • Liked: 665
  • Likes Given: 46
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #11 on: June 23, 2021, 04:39:44 AM »
good analysis folks, thanks.

Also, do not take beta carotene if you are a smoker. They had to stop a study on using for heart and cancer, and had to halt the study cause all the smokers started dieing.

You would think it would be better to stop the smokers from smoking than to stop a study .... :)

Human Habitat Index

  • Frazil ice
  • Posts: 474
    • View Profile
  • Liked: 51
  • Likes Given: 373
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #12 on: July 21, 2021, 04:02:57 AM »
Prof. Thomas Seyfried - 'Cancer as a Metabolic Disease: Implications for Novel Therapies'

There is a principle which is a bar against all information, which cannot fail to keep a man in everlasting ignorance. That principle is contempt prior to investigation. - Herbert Spencer

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #13 on: November 18, 2021, 09:44:35 PM »
re-post of a study write up that got lost. will leave it here, so it can still show in a cancer search.

"Palmitic acid promotes cancer metastasis and leaves a more aggressive “memory” in tumour cells.

Researchers at IRB Barcelona publish in the journal Nature the mechanism by which dietary palmitic acid (and not oleic or linoleic acid) favours tumour expansion.

(authors) have described the mechanism by which a diet rich in palmitic acid makes tumour cells more aggressive, conferring them a greater capacity to metastasize.

The authors have identified several “memory” markers left in tumour cells after exposure to palmitic acid: a change that causes cells to conserve greater metastatic capacity, even months after exposure to the fatty acid and that it could be related to a greater capacity of these tumor cells to promote innervation.

“In 2017, we published a study indicating that palmitic acid correlates with increased risk of metastasis, but we didn’t know the mechanism responsible for this. In this study, we detail the process and reveal the involvement of a metastatic capacity “memory” factor and we point to a therapeutic approach to reverse it. This is promising,”

This work has been carried out using the latest single-cell RNA sequencing and positional RNA sequencing technologies, which have allowed detailed characterisation of the composition of the distinct cells that form the tumour. This is one of the first times that positional RNA-sequencing technology has been used to study the cell composition of metastases."

https://www.irbbarcelona.org/en/news/scientific/palmitic-acid-promotes-cancer-metastasis-and-leaves-more-aggressive-memory-tumour

Nature (2021) DOI: 10.1038/s41586-021-04075-0

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #14 on: May 01, 2022, 09:17:44 AM »
Meet the plant virus that may help cure cancer
April 29, 2022

"Not all viruses are bad, and one in particular may have the power to stop cancer. Researchers at the University of California-San Diego are studying how a plant virus called cowpea mosaic virus stops cancer and prevents it from coming back. Their latest research shows that when the virus infects cancerous cells, it signals to the immune system and extends the anti-cancer response toward the tumor.

Cowpea mosaic virus is an infectious plant virus that commonly targets legumes. For the past seven years, however, study authors have been using animal models to determine its potential as a cancer immunotherapy treatment.

“This study helps validate the cowpea mosaic plant virus nanoparticle as our lead cancer immunotherapy candidate,” Nicole Steinmetz, a professor of nanoengineering at the UC San Diego Jacobs School of Engineering and the director of the Center for NanoImmunoEngineering, in a university release. “Now we have mechanistic data to explain why it is the most potent candidate, which further de-risks it for clinical translation.”
The perfect bait for fighting cancer?

The team has studied the cowpea mosaic virus in the form of nanoparticles. They injected the nanoparticles directly into the tumor to serve as bait for the immune system. Once the lure is set, immune cells detect the viral nanoparticles and send alarms to the rest of the immune system of a foreign invader in the body. While the immune cells build up to fight the virus, they start to eliminate the cancerous cells once they realize cowpea mosaic virus is inside a tumor.

Not only does the virus help get rid of the existing tumor, but Dr. Steinmetz notes that it also triggers a systemic immune response against any future tumors. While not studied in humans yet, they have observed this immune effect in canines and mouse models of various types of cancer. The cowpea mosaic virus is also unique in that it triggers an anti-cancer response that scientists don’t see in other plant viruses or virus-like particles.

“We’ve shown that it works, and now we need to show what makes it so special that it can induce this kind of response,” says lead author Veronique Beiss, a former postdoctoral researcher in Dr. Steinmetz’s lab. “That’s the knowledge gap we’re looking to fill.”
The virus triggers more disease-killing inflammation

To look at anti-tumor efficacy in similar plant viruses, the team compared the cowpea mosaic viruses with two plant viruses from the same family with similar shapes and sizes. The cowpea severe mosaic virus shared a similar RNA sequence and protein makeup. The other plant virus, the tobacco ringspot virus, only had a similar structure.

They then infected a melanoma tumor in mice with three doses of each virus-based nanoparticle immunotherapy given a week apart. Mice receiving the cowpea mosaic virus nanoparticles were more likely to survive and have the smallest tumors than those that did not. The tumor growth stopped about four days after the second dose.

Afterward, the researchers took immune cells from the spleen and lymph nodes from mice. They found that all plant viruses contain a protein shell to activate toll-like receptors that are on the surface of immune cells. However, the cowpea mosaic virus takes an extra step by using its RNA to activate an extra toll-like receptor. Activating additional toll-like receptors leads to more pro-inflammatory proteins called cytokines appearing and strengthening the immune response against cancer.

Another way the cowpea mosaic virus increases the immune response is by extending the cytokine response.

“We don’t see this with the other two plant viruses. The cytokine levels peak quickly, then go down and are gone,” explains Beiss. “This prolonged immune response is another key difference that sets cowpea mosaic virus apart.”

The study is published in the journal Molecular Pharmaceutics.

https://www.studyfinds.org/plant-virus-may-cure-cancer/


Cowpea Mosaic Virus Outperforms Other Members of the Secoviridae as In Situ Vaccine for Cancer Immunotherapy

In situ vaccination for cancer immunotherapy uses intratumoral administration of small molecules, proteins, nanoparticles, or viruses that activate pathogen recognition receptors (PRRs) to reprogram the tumor microenvironment and prime systemic antitumor immunity. Cowpea mosaic virus (CPMV) is a plant virus that─while noninfectious toward mammals─activates mammalian PRRs. Application of CPMV as in situ vaccine (ISV) results in a potent and durable efficacy in tumor mouse models and canine patients; data indicate that CPMV outperforms small molecule PRR agonists and other nonrelated plant viruses and virus-like particles (VLPs). In this work, we set out to compare the potency of CPMV versus other plant viruses from the Secoviridae. We developed protocols to produce and isolate cowpea severe mosaic virus (CPSMV) and tobacco ring spot virus (TRSV) from plants. CPSMV, like CPMV, is a comovirus with genome and protein homology, while TRSV lacks homology and is from the genus nepovirus. When applied as ISV in a mouse model of dermal melanoma (using B16F10 cells and C57Bl6J mice), CPMV outperformed CPSMV and TRSV─again highlighting the unique potency of CPMV. Mechanistically, the increased potency is related to increased signaling through toll-like receptors (TLRs)─in particular, CPMV signals through TLR2, 4, and 7. Using knockout (KO) mouse models, we demonstrate here that all three plant viruses signal through the adaptor molecule MyD88─with CPSMV and TRSV predominantly activating TLR2 and 4. CPMV induced significantly more interferon β (IFNβ) compared to TRSV and CPSMV; therefore, IFNβ released upon signaling through TLR7 may be a differentiator for the observed potency of CPMV-ISV. Additionally, CPMV induced a different temporal pattern of intratumoral cytokine generation characterized by significantly increased inflammatory cytokines 4 days after the second of 2 weekly treatments, as if CPMV induced a “memory response”. This higher, longer-lasting induction of cytokines may be another key differentiator that explains the unique potency of CPMV-ISV."

https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.2c00058

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #15 on: May 06, 2022, 08:06:51 PM »
A Significant Question in Cancer Risk and Therapy: Are Antibiotics Positive or Negative Effectors?
Current Answers and Possible Alternatives
Received: 31 July 2020; Accepted: 31 August 2020; Published: 6 September 2020


Abstract: Cancer is predominantly considered as an environmental disease caused by genetic or
epigenetic alterations induced by exposure to extrinsic (e.g., carcinogens, pollutants, radiation) or
intrinsic (e.g., metabolic, immune or genetic deficiencies). Over-exposure to antibiotics, which is
favored by unregulated access as well as inappropriate prescriptions by physicians, is known to have
led to serious health problems such as the rise of antibiotic resistance, in particular in poorly developed
countries. In this review, the attention is focused on evaluating the effects of antibiotic exposure on
cancer risk and on the outcome of cancer therapeutic protocols, either directly acting as extrinsic
promoters, or indirectly, through interactions with the human gut microbiota. The preponderant
evidence derived from information reported over the last 10 years confirms that antibiotic exposure
tends to increase cancer risk and, unfortunately, that it reduces the efficacy of various forms of cancer
therapy (e.g., chemo-, radio-, and immunotherapy alone or in combination). Alternatives to the
current patterns of antibiotic use, such as introducing new antibiotics, bacteriophages or enzybiotics,
and implementing dysbiosis-reducing microbiota modulatory strategies in oncology, are discussed.
The information is in the end considered from the perspective of the most recent findings on the
tumor-specific and intracellular location of the tumor microbiota, and of the most recent theories
proposed to explain cancer etiology on the notion of regression of the eukaryotic cells and systems
to stages characterized for a lack of coordination among their components of prokaryotic origin,
which is promoted by injuries caused by environmental insults


snip:
3. Antibiotics and Cancer Risk
As correctly expressed by McCormack and Boffetta in the title of one of their articles (“Today’s
lifestyles, tomorrow’s cancers: trends in lifestyle risk factors for cancer in low- and middle-income
countries”) [110 ], the reality is that it is precisely in those countries where not only the unregulated
consumption of antibiotics happens more frequently, but also where, unlike what happens in developed
counties [ 111 ], accurate records of cancer incidence are not periodically updated or not even maintained
at all. Given this situation, epidemiological assessments about antibiotic exposure and cancer risk are
very valuable. In the course of the last fifteen years, studies on possible effects of antibiotic exposure
on cancer risk have focused primarily on the cancer types more frequent in humans, and generally
have been designed to include cohorts of cancer patients and randomly selected non-cancer patients
as controls.
In studies related to breast cancer, the data suggested an association between antibiotic
consumption and cancer risk. Although in some studies the association was qualified as weak [112 , 113 ],
other studies reported a clearly positive association with the number of prescriptions and the cumulative
days of antibiotic use [114 ,115 ]. While in some studies the same patterns of association were observed
with all classes of antibiotics tested [ 114 ,115 ], a better association was reported by different antibiotic
classes [112 , 116 ]. The situation was not clear with regard to lung cancer, as the data provided insufficient
evidence to support or refute a possible carcinogenic effect of antibiotics [117]. The information from
studies on colorectal cancer (CRC) seems more conclusive, most likely due to the greater number of
studies published much more frequently because of the general trend of increased scientific interest
in the gut microbiota. Most CRC-related studies report an association, even at the adenoma stage,
with both timing and duration of antibiotic exposure [ 118 – 120 ]. In addition, and more importantly,
some of these studies allowed the dissociation between the effects of antibiotic usage on the risk of
colon cancer vs. rectal cancer, as the data consistently showed a positive association between antibiotic
use and colon cancer, but there was either no association or a negative correlation with cancer of the
rectum [121–123].
In more general studies of other digestive cancers (esophagus, stomach, small intestine,
hepatobiliary, and pancreas), positive associations were found between certain antibiotic classes
and particular tumor types, which increased with dose [124 , 125]. Positive associations were found
between the use of penicillins and esophageal, gastric and pancreatic cancer, with clearer dose-response
effects in the latter type [124 ]. Nitroimidazoles and quinolones showed more modest associations
with all digestive tumor types investigated [125 ]. Studies on non-melanoma skin cancer showed
that there was an increased risk of developing skin cancer associated with the use of photosensitive
antibiotics [ 126– 130 ]. Exposure to antibiotics such as ciprofloxacin, ketoconazole, and sulfamethoxazole
increased the risk of developing basal cell carcinoma (BCC), whereas the use of doxycycline and
sulfamethoxazole increased the risk of squamous cell carcinoma (SCC) [126 , 127 ,129 ]. Although some
studies associated the use of tetracycline with BCC risk [126 ,127 ], it was also reported that the use of
tetracycline demonstrated positive interactions regarding simultaneous UV light exposure and the risk
of SCC [129 ]. An association was also observed between the use of moxifloxacin and an increased
risk of developing SCC during the first year after lung post-transplantation [ 128 ]. In addition, the use
of a mathematical model also predicted, and somehow confirmed, that the risk of developing skin
cancer is positively associated with the use of antibiotics [130 ]. Finally, two large multi-tumor type
studies [ 131 ,132 ] are worthwhile mentioning. In the first one [ 131 ], researchers followed for a period
of six years the number of cancers diagnosed in a sample of 3,112,624 individuals with no previous
history of cancer, and analyzed that information with regard to the patterns of antibiotic usage in the
study population. Data from this study showed that cancer incidence increased with the number
of prescriptions, and that the extent of the association of the relative risk with antibiotic exposure
varied with tumor type, being greatest in tumors of endocrine glands, followed in decreasing order by
cancers of the prostate, breast, lung, colon and ovary [ 131 ]. The second multi-tumor type study [ 132 ],
the largest reported to date, reported results from the systemic review of about 7.9 million individuals
Antibiotics 2020, 9, 580 8 of 19
showing that, on average, antibiotic use increased cancer risk by about 18%, although the effect varied
with tumor type: 30% increased incidence of lung, pancreatic and genitourinary cancers; smaller risk
increases (6–8%) for CRC, gastric cancer and melanoma; and no association was found with esophageal
or cervical cancer. With regard to antibiotic types, the highest risk was associated with the use of
β-lactams, cephalosporins and fluoroquinolones"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558931/pdf/antibiotics-09-00580.pdf


Lynn Margulis and the endosymbiont hypothesis: 50 years later

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426843/

(tripped across this while reading some astrobio, so leaving it here)

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #16 on: May 25, 2022, 01:39:39 AM »
CF33-hNIS-antiPDL1 for the Treatment of Metastatic Triple Negative Breast Cancer (cancer virus)

This phase I trial tests the safety, side effects, and best dose of CF33-hNIS-antiPDL1 in treating patients with triple negative breast cancer that has spread to other places in the body (metastatic). CF33-hNIS-antiPDL1 is an oncolytic virus. This is a virus that is designed to infect tumor cells and break them down. "



PRIMARY OBJECTIVE:

I. To determine the safety and tolerability of a novel chimeric oncolytic orthopoxvirus, oncolytic virus CF33-expressing hNIS/Anti-PD-L1 antibody (CF33-hNIS-antiPDL1), by the evaluation of toxicities including: type, frequency, severity, attribution, time course, reversibility and duration according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria.

SECONDARY OBJECTIVES:

I. To determine the optimal biologic dose (OBD) (defined as a safe dose that induces an immune response in tumors [increase checkpoint target PD-L1 by at least 5% and/or increase T cell infiltration by at least 10%]) and the recommended phase II dose (RP2D) for future expansion trial.

II. To determine tumor response rates by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (primary) and immune-modified (i)RECIST (secondary).

III. To document possible therapeutic efficacy and evaluate progression-free survival, overall survival and response.

EXPLORATORY OBJECTIVE:

I. To determine the immune and genomic profiles of tumors before and after CF33-hNIS-antiPDL1 therapy.

OUTLINE: This is a dose-escalation study.

Patients receive CF33-hNIS-antiPDL1 intratumorally (IT) on days 1 and 15. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year

https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2021-08983

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #17 on: April 16, 2023, 08:32:07 PM »

Tiny DNA circles are key drivers of cancer, Stanford Medicine-led international study finds. (April 12, 2023)

Tiny circles of DNA harbor cancer-associated oncogenes and immunomodulatory genes promoting cancer development. They arise during transformation from pre-cancer to cancer, say Stanford Medicine-led team.

(...)
“When we think about how a tumor evolves in a patient and in response to treatment, we think of the branching trees of life proposed by Charles Darwin,” Mischel said. “This idea is so powerful that researchers often sequence the DNA from multiple parts of a tumor and draw these trees to learn about its evolution. If a mutation is there at the trunk of the tree and in all of its branches, we assume it is a key driver event in the formation of the tumor; if it is in only some branches, we assume it happened later in tumor development and may not be a good target for drug development.”

But these assumptions hinge on the idea that all of a tumor’s DNA is neatly contained on chromosomes, which are evenly divided among daughter cells each time a cancer cell divides — ensuring that each new cell gets one, and only one, copy of each chromosome.

In contrast, the tiny ecDNA circles swirl in a dividing cell like bubbles circling a bathtub drain and are portioned willy-nilly between the new daughter cells. One may get nearly all the circles; the other, almost none. As the generations accumulate, the evolutionary tree favored by Darwin begins to look decidedly odd, with the appearance of ecDNA-bearing cells sprinkled among the branches like haphazardly hung Christmas lights.

“Some researchers have looked at the evolutionary trees and decided that, because you see it here, but not there, it must be that ecDNA formation is a late event and probably isn’t important when considering treatments,” Mischel said. “Our team thought that interpretation was wrong.”
Pinpointing a reason

To get to the bottom of the tiny circles, Mischel, Chang and their collaborators turned to a specific example of cancer development — people with a condition known as Barrett’s esophagus, which occurs when the cells lining the lower part of the esophagus are damaged by acid reflux and become more like cells lining the intestine than healthy esophageal tissue. About 1% of these people develop esophageal cancer, which is difficult to treat and has a high mortality rate. Because the outcome is so poor, people with Barrett’s esophagus are routinely monitored with endoscopies and biopsies of the abnormal tissue. Because of these frequent biopsies, the researchers had access to tissue samples collected both before and after cancers developed.

The researchers assessed the prevalence of ecDNA, and identified the genes they carried, in biopsies from nearly 300 people with Barrett’s esophagus or esophageal cancer treated at the University of Cambridge or at Seattle’s Fred Hutchison Cancer Center, where individual patients were studied as the cancer developed. They found that the prevalence of ecDNA increased from 24% to 43% in early- versus late-stage esophageal cancer, indicating the continual formation of the DNA circles during cancer progression. More tellingly, they found that 33% of people with Barrett’s esophagus who developed esophageal cancer had ecDNA in their precancerous cells. In contrast, only one out of 40 people who didn’t develop cancer had cells with ecDNA, and that individual passed away due to another cause.

“The conclusions were remarkable,” Mischel said. “We see that ecDNA can arise in these precancerous cells, and that if it is there, the patient is going to get cancer. We also saw the continuous formation of ecDNA as the cancer progresses, indicating that it is advantageous to cancer growth. Finally, we saw that the ecDNA can contain immune-modulatory genes in addition to oncogenes.”

https://med.stanford.edu/news/all-news/2023/04/ecDNA-cancer.html?sf176823295=1

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #18 on: April 21, 2023, 06:30:32 PM »


The complete set of T cell receptors in an individual carries evidence of both past and current immune responses. These traces can act as biomarkers for diseases mediated by the immune system, such as infectious diseases, autoimmune disorders, and cancer. Recent technological advancements enable us to sequence T cell receptors from patients. Nonetheless, only a small number of sequenced T cell receptors from a patient are expected to contain traces relevant to a specific disease. In this repository, we introduce the latest source code for our method to identify these traces.
(...)
In this repository, we present several examples illustrating our method for identifying immune traces that can serve as biomarkers. Each example is self-contained, complete with the associated datasets required to re-run the model. Some results are successful, while others are not (perhps there are bugs in the code). Our examples demonstrate the ability to:

    distinguish malignant from non-malignant ovarian tissue,
    diagnose breast cancer from peripheral blood,
    predict clearance of preneoplastic cervical lesions,
    and provide an example where our code performed poorly.

Publications

    Cervical Cancer Screening
    Ovarian Cancer
    Breast and Colorectal Cancer
    Multiple Sclerosis


https://github.com/jostmey/msm

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #19 on: August 31, 2023, 07:58:01 PM »
Taking dietary supplements full of antioxidants could actually help cancerous tumors grow

Taking vitamins or dietary supplements could be feeding tumors and promote their growth, scientists warn. Common antioxidants, such as vitamins A, C, selenium, and zinc, can stimulate the growth of blood vessels in cancer when taken in excess. This discovery surprised researchers, as prior studies have shown antioxidants to be protective. While Swedish scientists state that natural levels of antioxidants in food are safe, taking supplements containing additional antioxidants could fuel tumor growth and allow the disease to spread faster.

The study, conducted by a team at the Karolinska Institutet, concludes that vitamin C and other antioxidants promote the formation of new blood vessels within lung cancer tumors. Study authors suggest that this finding could be applicable to all cancers and their spread.

“We’ve found that antioxidants activate a mechanism that causes cancer tumors to form new blood vessels, which is surprising, since it was previously thought that antioxidants have a protective effect,
(more)

https://studyfinds.org/dietary-supplements-help-tumors/


Antioxidants stimulate BACH1-dependent tumor angiogenesis

Abstract

Lung cancer progression relies on angiogenesis, which is a response to hypoxia typically coordinated by hypoxia-inducible transcription factors (HIFs); but growing evidence indicate that transcriptional programs beyond HIFs control tumor angiogenesis. Here we show that the redox-sensitive transcription factor BTB and CNC homology 1 (BACH1) controls the transcription of a broad range of angiogenesis genes. BACH1 is stabilized by lowering reactive oxygen species levels; consequently, angiogenesis gene expression in lung cancer cells, tumor organoids, and xenograft tumors increased substantially following vitamin C and E and N-acetylcysteine administration in a BACH1-dependent fashion under normoxia. Moreover, angiogenesis gene expression increased in endogenous BACH1–overexpressing cells and decreased in BACH1-knockouts in the absence of antioxidants. BACH1 levels also increased upon hypoxia and following administration of prolyl hydroxylase inhibitors in both HIF1a-knockout and wild-type cells. BACH1 was found to be a transcriptional target of HIF1α but BACH1’s ability to stimulate angiogenesis gene expression was HIF1a independent. Antioxidants increased tumor vascularity in vivo in a BACH1-dependent fashion, and overexpressing BACH1 rendered tumors sensitive to anti-angiogenesis therapy. BACH1 expression in tumor sections from lung cancer patients correlates with angiogenesis gene and protein expression. We conclude that BACH1 is an oxygen- and redox-sensitive angiogenesis transcription factor.

https://www.jci.org/articles/view/169671

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #20 on: November 26, 2023, 09:47:36 AM »
( i missed this when it came out, just popped up on HN, and is a interesting study back in 2019. Even dosages are wild.)


Doxycycline, Azithromycin and Vitamin C (DAV): A potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs)

Abstract

Here, we devised a new strategy for eradicating cancer stem cells (CSCs), via a “synthetic-metabolic” approach, involving two FDA-approved antibiotics and a dietary vitamin supplement. This approach was designed to induce a “rho-zero-like” phenotype in cancer cells. This strategy effectively results in the synergistic eradication of CSCs, using vanishingly small quantities of two antibiotics. The 2 metabolic targets are i) the large mitochondrial ribosome and ii) the small mitochondrial ribosome. Azithromycin inhibits the large mitochondrial ribosome as an off-target side-effect. In addition, Doxycycline inhibits the small mitochondrial ribosome as an off-target side-effect. Vitamin C acts as a mild pro-oxidant, which can produce free radicals and, as a consequence, induces mitochondrial biogenesis. Remarkably, treatment with a combination of Doxycycline (1 μM), Azithromycin (1 μM) plus Vitamin C (250 μM) very potently inhibited CSC propagation by >90%, using the MCF7 ER(+) breast cancer cell line as a model system. The strong inhibitory effects of this DAV triple combination therapy on mitochondrial oxygen consumption and ATP production were directly validated using metabolic flux analysis. Therefore, the induction of mitochondrial biogenesis due to mild oxidative stress, coupled with inhibition of mitochondrial protein translation, may be a new promising therapeutic anti-cancer strategy. Consistent with these assertions, Vitamin C is known to be highly concentrated within mitochondria, by a specific transporter, namely SVCT2, in a sodium-coupled manner. Also, the concentrations of antibiotics used here represent sub-antimicrobial levels of Doxycycline and Azithromycin, thereby avoiding the potential problems associated with antibiotic resistance. Finally, we also discuss possible implications for improving health-span and life-span, as Azithromycin is an anti-aging drug that behaves as a senolytic, which selectively kills and removes senescent fibroblasts.

Keywords: Doxycycline, Azithromycin, Vitamin C, combination therapy, mitochondrial ATP depletion, glycolysis

(more)



morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #21 on: November 30, 2023, 07:04:36 AM »
( i am speechless bout this one, the second one seems simpler)



Left-sided Cancer: Blame your bed and TV?       By R. Douglas Fields on July 2, 2010

Curiously, the cancer rate is 10 percent higher in the left breast than in the right. This left-side bias holds true for both men and women and it also applies to the skin cancer melanoma. Researchers Örjan Hallberg of Hallberg Independent Research in Sweden and Ollie Johansson of The Karolinska Institute in Sweden, writing in the June issue of the journal Pathophysiology, suggest a surprising explanation that not only points to a common cause for both cancers, it may change your sleeping habits.


For unknown reasons the rates of breast cancer and melanoma have both increased steadily in the last 30 years. Exposure to the sun elevates the risk of melanoma, but the sun's intensity has not changed in the last three decades. Stranger still, melanoma most commonly affects the hip, thighs and trunk, which are areas of the body protected from the sun. What is responsible for the left-side dominance and increasing incidence of these cancers?


An intriguing clue comes from the Far East. In Japan there is no correlation between the rates of melanoma and breast cancer as there is in the West, and there is no left-side prevalence for either disease. Moreover, the rate of breast cancer in Japan is significantly lower than in the West; only 3 percent of what is seen in Sweden, for example. The rate of prostate cancer in Japan is only 10 percent of that in the U.K. and U.S.


The researchers suggest an explanation based on differences in sleeping habits in Japan and Western countries. Previous research has shown that both men and women prefer to sleep on their right sides. The reasons for this general preference are unclear, but sleeping on the right side may reduce the weight stress on the heart, and the heartbeat is not as loud as when sleeping on the left. Still, there is no reason to suspect that people in Japan sleep in positions that are any different from those in the West. The beds in Japan, however, are different. The futons used for sleeping in Japan are mattresses placed directly on the bedroom floor, in contrast to the elevated box springs and mattress of beds used in the West. A link between bedroom furniture and cancer seems absurd, but this, the researchers conclude, is the answer.


The first line of evidence they cite comes from a 2007 study in Sweden conducted between 1989 and 1993 that revealed a strong link between the incidence of melanoma and the number of FM and TV transmission towers covering the area where the individuals lived. Despite epidemiological correlations like this one suggesting the possibility that electromagnetic radiation from FM and TV broadcasts stations could suppress the immune system and promote cancer, the strength of these electromagnetic fields is so feeble it has been difficult to imagine any biological basis for the correlation.


Consider, however, that even a TV set cannot respond to broadcast transmissions unless the weak electromagnetic waves are captured and amplified by an appropriately designed antenna. Antennas are simply metal objects of appropriate length sized to match the wavelength of a specific frequency of electromagnetic radiation. Just as saxophones are made in different sizes to resonate with and amplify particular wavelengths of sound, electromagnetic waves are selectively amplified by metal objects that are the same, half or one quarter of the wavelength of an electromagnetic wave of a specific frequency. Electromagnetic waves resonate on a half-wavelength antenna to create a standing wave with a peak at the middle of the antenna and a node at each end, just as when a string stretched between two points is plucked at the center. In the U.S. bed frames and box springs are made of metal, and the length of a bed is exactly half the wavelength of FM and TV transmissions that have been broadcasting since the late 1940s. In Japan most beds are not made of metal, and the TV broadcast system does not use the 87- to 108-megahertz frequency used in Western countries.
(...)
https://blogs.scientificamerican.com/guest-blog/left-sided-cancer-blame-your-bed-and-tv/


(oops, lost the one on lidocaine stimulating apotasis in head , neck and mouth cancers. Nature)

oren

  • First-year ice
  • Posts: 9860
    • View Profile
  • Liked: 3609
  • Likes Given: 4096
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #22 on: December 02, 2023, 08:31:01 PM »
Cancer in Sweden correlated with broadcast stations. In the US beds are made from metal. These data items are unrelated and cannot be an explanation.
What if BRCA and similar mutations are less prevalent in Japan, that could explain the difference from Sweden much more easily?

Human Habitat Index

  • Frazil ice
  • Posts: 474
    • View Profile
  • Liked: 51
  • Likes Given: 373
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #23 on: December 05, 2023, 07:05:42 AM »
"The most important thing to remember is that cancer is a disease of toxicity. The best way to achieve a true cure, therefore, is to address this underlying cause. Recognizing that a tumor is an ally, not an enemy, makes it possible to work to promote its function so it will no longer be needed."

https://www.westonaprice.org/health-topics/modern-diseases/god-create-cancer/?fbclid=IwAR3VomNF5j4u3n-L1n5tRGkY93D2_acd5lN_XVq0d32jLrkAExA9AFPchRI#gsc.tab=0 :D
There is a principle which is a bar against all information, which cannot fail to keep a man in everlasting ignorance. That principle is contempt prior to investigation. - Herbert Spencer

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #24 on: December 05, 2023, 06:42:17 PM »
Is an older study, but seemed odd to me too. They do point out that they measured it?

Back in 2k, i seem to remember one with a linkage to electric blanket use in US and UK too. Seem to recall they point out that in eastern Euro?, they used 12v heating mattress pads instead.

kassy

  • First-year ice
  • Posts: 8701
    • View Profile
  • Liked: 2069
  • Likes Given: 2007
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #25 on: December 05, 2023, 07:57:01 PM »
"The most important thing to remember is that cancer is a disease of toxicity. The best way to achieve a true cure, therefore, is to address this underlying cause. Recognizing that a tumor is an ally, not an enemy, makes it possible to work to promote its function so it will no longer be needed."

https://www.westonaprice.org/health-topics/modern-diseases/god-create-cancer/?fbclid=IwAR3VomNF5j4u3n-L1n5tRGkY93D2_acd5lN_XVq0d32jLrkAExA9AFPchRI#gsc.tab=0 :D

That is such drivel. If breast cancer genes run in your family you can die really really young compared people in the same environment and that is just one simple example.
Þetta minnismerki er til vitnis um að við vitum hvað er að gerast og hvað þarf að gera. Aðeins þú veist hvort við gerðum eitthvað.

Human Habitat Index

  • Frazil ice
  • Posts: 474
    • View Profile
  • Liked: 51
  • Likes Given: 373
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #26 on: December 05, 2023, 11:55:14 PM »
"The most important thing to remember is that cancer is a disease of toxicity. The best way to achieve a true cure, therefore, is to address this underlying cause. Recognizing that a tumor is an ally, not an enemy, makes it possible to work to promote its function so it will no longer be needed."

https://www.westonaprice.org/health-topics/modern-diseases/god-create-cancer/?fbclid=IwAR3VomNF5j4u3n-L1n5tRGkY93D2_acd5lN_XVq0d32jLrkAExA9AFPchRI#gsc.tab=0 :D

That is such drivel. If breast cancer genes run in your family you can die really really young compared people in the same environment and that is just one simple example.

Would they live longer if they avoided toxins ?
There is a principle which is a bar against all information, which cannot fail to keep a man in everlasting ignorance. That principle is contempt prior to investigation. - Herbert Spencer

vox_mundi

  • Multi-year ice
  • Posts: 10601
    • View Profile
  • Liked: 3546
  • Likes Given: 770
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #27 on: December 19, 2023, 04:23:10 PM »
Massive Drug Search Uncovers Infinitesimal Molecule That Kills Cancers While Sparing Immune Cells
https://medicalxpress.com/news/2023-12-massive-drug-uncovers-infinitesimal-molecule.html

Scientists have found an experimental small molecule that induces a form of cell death to kill a variety of cancers while enhancing the power of the immune system and leaving healthy cells totally unscathed.

The molecule triggers ferroptosis, a unique form of cell death that is increasingly being tested as an anti-cancer strategy. The international team of scientists have reported their findings in the journal Science Translational Medicine.

... Even though ferroptosis is being actively pursued as a potential cancer treatment, other researchers are studying the process for its pathological role in a variety of disparate diseases that range from Alzheimer's, cardiovascular disease to even various forms of cancer. Ferroptosis is intimately involved in the disease processes of these conditions, studies have shown.

In terms of harnessing this form of cell death as a therapeutic, teams worldwide are racing to overcome a number of conundrums, especially what's known as the "non-selective" activities of ferroptotic cell death. It doesn't just kill cancer cells, it kills a multitude of cells in the immediate micro-environment, particularly the Big Three: dendritic cells, T cells and neutrophils, which seemingly defeats the promise that ferroptosis holds as a cancer fighter.

That means most compounds capable of inducing ferroptosis in cancer cells may also inflict the same fate on various immune cells, weakening the immune system's ability to swoop in and wage war on deadly tumors.

Now, Li and a far-flung team of collaborators on three continents have pinpointed a promising small molecule called N6F11, which not only triggers ferroptotic cell death, it also selectively causes the degradation of glutathione peroxidase-4, also known as GPX4, a notorious blocker of ferroptosis.

Li and colleagues, who went on a wide-ranging drug hunt, screening a slew of compounds to find N6F11 and its unique properties, say with N6F11 in the mix, ferroptosis can be triggered and GPX4 is no longer in the way to prevent this specialized form of cell death from annihilating tumors. Even more eye-opening, N6F11 degraded GPX4 in human pancreatic, bladder, breast, and cervical cancer cells without affecting GPX4 in that vital trio of the immune system: dendritic cells, T cells and neutrophils.

Li, along with colleagues from Columbia University in New York, Université de Paris in France, a large team at UT Southwestern Medical Center in Dallas and beyond, also found that N6F11 slowed the growth of active tumors in mouse models inoculated with pancreatic cancer cells. The animals endured the treatment without severe side effects—an effect the authors tied to N6F11's ability to stimulate T cells.

Jingbo Li et al, Tumor-specific GPX4 degradation enhances ferroptosis-initiated antitumor immune response in mouse models of pancreatic cancer, Science Translational Medicine (2023)
https://www.science.org/doi/10.1126/scitranslmed.adg3049

... Inducing ferroptotic cell death is an emerging treatment for cancer; however, because of its non-selective properties, it can also inhibit the immune cells. To overcome this, Li et al. have identified a small molecule compound, N6F11, that selectively triggered degradation of glutathione peroxidase 4 (GPX4), a ferroptosis repressor, in tumor cells and not immune cells. The authors further tested this in mouse models of pancreatic cancer, demonstrating that treatment increased sensitivity to immune checkpoint blockade (ICB). These preclinical results warrant further study of N6F11 and its potential benefit to improve efficacy of ICB in patients with cancer.
There are 3 classes of people: those who see. Those who see when they are shown. Those who do not see

Insensible before the wave so soon released by callous fate. Affected most, they understand the least, and understanding, when it comes, invariably arrives too late

Fiat iustitia, et pereat mundus

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #28 on: December 26, 2023, 10:41:53 PM »
Just wanted to drop this here as related to the bed story above. Saw this back when it came out in 2015, but it just popped up again on Hacker News, so thought would tack it on to the story...Sketchy paper, sketchy journal, but interesting)

The effects of grounding (earthing) on inflammation, the immune response, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases
(...)
Summary of findings to date

Grounding appears to improve sleep, normalize the day–night cortisol rhythm, reduce pain, reduce stress, shift the autonomic nervous system from sympathetic toward parasympathetic activation, increase heart rate variability, speed wound healing, and reduce blood viscosity. A summary has been published in the Journal of Environmental and Public Health.4
Effects on sleep

One of the first published grounding studies examined the effects of grounding on sleep and circadian cortisol profiles.5 The study involved 12 subjects who were in pain and had problems sleeping. They slept grounded for 8 weeks using the system shown in Figure 4. During this period, their diurnal cortisol profiles normalized, and most of the subjects reported that their sleep improved and their pain and stress levels declined.
An external file that holds a picture, illustration, etc. Object name is jir-8-083Fig4.jpg
Figure 4

Grounded sleep system.

Notes: Grounded sleep system consists of a cotton sheet with conductive carbon or silver threads woven into it. The threads connect to a wire that leads out the bedroom window or through the wall to a metal rod inserted into the Earth near a healthy plant. Alternatively, it can be connected to the ground terminal of an electrical outlet. Sleeping on this system connects the body to the Earth. A frequent report from people using this system is that sleeping grounded improves the quality of sleep and reduces aches and pains from a variety of causes.

The results of the experiment led to these conclusions: 1) grounding the body during sleep yields quantifiable changes in diurnal or circadian cortisol secretion levels that, in turn, 2) produce changes in sleep, pain, and stress (anxiety, depression, and irritability), as measured by subjective reporting. The cortisol effects described by Ghaly and Teplitz5 are particularly significant in the light of recent research showing that prolonged chronic stress results in glucocorticoid receptor resistance.6 Such resistance results in failure to downregulate inflammatory responses, which can thereby increase risks of a variety of chronic diseases.
(more)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378297/


Human Habitat Index

  • Frazil ice
  • Posts: 474
    • View Profile
  • Liked: 51
  • Likes Given: 373
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #29 on: December 27, 2023, 10:21:27 AM »
   Fitzgerald Report to US Congress found conspiracy to suppress cancer cures.   


There is a principle which is a bar against all information, which cannot fail to keep a man in everlasting ignorance. That principle is contempt prior to investigation. - Herbert Spencer

vox_mundi

  • Multi-year ice
  • Posts: 10601
    • View Profile
  • Liked: 3546
  • Likes Given: 770
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #30 on: January 31, 2024, 05:23:38 PM »
Precursor of Cholesterol Protects Cells From ferroptosis, Study Finds
https://medicalxpress.com/news/2024-01-precursor-cholesterol-cells-ferroptosis.html

In a groundbreaking study, a team led by Würzburg Professor José Pedro Friedmann Angeli has shown that the cholesterol precursor 7-dehydrocholesterol (7-DHC) plays a crucial role as an antioxidant: it integrates into the cell membranes and protects the cells by preventing a certain type of cell death, known as ferroptosis.

"Until now, the accumulation of 7-DHC was only associated [with] neurodevelopmental defects, now we show that it actually increases cellular fitness and could promote a more aggressive behavior in cancers such as Burkitt's lymphoma and neuroblastoma," says Friedmann Angeli.

The newly discovered protective function of 7-DHC opens up exciting prospects for further improving the treatment of cancer and other diseases associated with ferroptosis. "It gives us new opportunities to test potential inhibitors that target cholesterol biosynthesis and are already established in medical practice."

Most studies focus on how cholesterol contributes directly to these diseases.

In this area, the discovery of the cholesterol precursor 7-DHC as an antioxidant opens up new possibilities: Studies on changes in 7-DHC levels could provide crucial new insights into the diseases. In addition, drugs that specifically block 7-DHC production should be researched in combination with other drugs—this could have a positive effect in the treatment of some cancers.

There are drugs authorized by the US Food and Drug Administration (FDA) that can inhibit the DHCR7 enzyme. These include trazodone, which is prescribed around 20 million times a year in the U.S., sometimes even for off-label use to treat insomnia.

"Studies have shown that people taking this drug have elevated plasma levels of 7-DHC. Epidemiological studies are crucial to better understand possible effects here," says Friedmann Angeli.

These studies would help to find out whether there is a connection between patient groups who regularly take ferroptosis-modulating drugs such as trazodone and cancer incidence, the occurrence of metastases or other critical aspects of public health.

José Angeli, 7-Dehydrocholesterol is an endogenous suppressor of ferroptosis, Nature (2024)
https://www.nature.com/articles/s41586-023-06878-9
There are 3 classes of people: those who see. Those who see when they are shown. Those who do not see

Insensible before the wave so soon released by callous fate. Affected most, they understand the least, and understanding, when it comes, invariably arrives too late

Fiat iustitia, et pereat mundus

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #31 on: February 05, 2024, 12:20:13 AM »
DNA damage and somatic mutations in mammalian cells after irradiation with a nail polish dryer

Experimental design and examination of cytotoxicity

To study the cytotoxic effect of irradiation by a UV-nail polish dryer, mouse embryonic fibroblasts (MEFs), human foreskin fibroblasts (HFFs), and adult human epidermal keratinocytes (HEKa) were exposed under several distinct conditions (Fig. 1). Each primary cell line was irradiated one, two, or three times, with the duration of each exposure lasting between 0 and 20 min. Cell viability was measured 48 hours after the final irradiation with each condition repeated at least three times. Analysis of cell viability revealed that UV radiation induced cytotoxicity with higher number of exposures causing a lower cell viability (Fig. 2a). For example, in all cell line models, a single 20-minute irradiation resulted in 20–30% cell death, while three consecutive 20-minute exposures caused between 65% and 70% cell death
(snip)
Indeed, prior studies have shown that UVA can generate low level of C > T somatic mutations consistent with pyrimidine-pyrimidine photodimers74. Intriguingly, in this study, we demonstrate that UVA with wavelengths between 365 and 395 nm, which is generally considered to be safe and is commonly used in a plethora of consumer products, causes DNA oxidative damage leading to C > A mutations; no evidence was found that radiation generated by the UV-nail polish machine generates any pyrimidine-pyrimidine photodimers (Supplementary Fig. 2). Importantly, the longer-wavelength of UVA emitted by a nail polish dryer (365–395 nm) will reach all layers of the epidermis and it will penetrate towards the deeper layers of the dermis, potentially, even affecting some skin stem cells71,72. As keratinocytes are present in all layers of the epidermis and melanocytes are found in the basal layer of epidermis, exposure to UVA from a nail polish dryer may irradiate these cells in a physiologically normal human skin.
(snip)
Experimental design and examination of cytotoxicity

To study the cytotoxic effect of irradiation by a UV-nail polish dryer, mouse embryonic fibroblasts (MEFs), human foreskin fibroblasts (HFFs), and adult human epidermal keratinocytes (HEKa) were exposed under several distinct conditions. Each primary cell line was irradiated one, two, or three times, with the duration of each exposure lasting between 0 and 20 min. Cell viability was measured 48 hours after the final irradiation with each condition repeated at least three times. Analysis of cell viability revealed that UV radiation induced cytotoxicity with higher number of exposures causing a lower cell viability. For example, in all cell line models, a single 20-minute irradiation resulted in 20–30% cell death, while three consecutive 20-minute exposures caused between 65% and 70% cell death.
(more)

https://www.nature.com/articles/s41467-023-35876-8

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #32 on: April 06, 2024, 10:22:52 AM »
 The cancer patients saw their tumours disappear after the treatment, and have been cancer-free for two years.

More than a dozen rectal cancer patients in the United States have seen their cancer disappear after undergoing experimental immunotherapy, in what doctors are calling an astonishing result.

A first in cancer treatment

The trial has been hailed as a first in cancer treatment, with one of the paper’s authors, Dr Luis Diaz Jr of Memorial Sloan Kettering, telling the New York Times that he knew of no other study in which a treatment completely obliterated a cancer in every patient.

“I believe this is the first time this has happened in the history of cancer,” he said.
(snip)
How does this immunotherapy work?

Inspiration for the study came from a previous trial led by Dr Diaz, which saw patients taking a drug called pembrolizumab, the New York Times reported. That trial, which involved patients with advanced cancer that resisted standard treatment, saw participants’ tumours stabilise, shrink and even vanish.

In the current trial, researchers wanted to see what a similar drug, dostarlimab, would do if used before the cancer cells had a chance to spread.

This sort of treatment focuses on particular proteins called checkpoints, which are made by some types of immune system cells as well as some cancer cells, according to the US National Cancer Institute. The checkpoints, which keep immune responses from being too strong, can sometimes prevent immune cells from effectively killing cancer cells.

Like pembrolizumab, dostarlimab is a “checkpoint inhibitor”: It essentially “releases the brakes” on an immune cell, freeing it to recognise and attack cancer cells, according to MSK.

“When the brakes are taken off the immune cells, MMRd cells look especially strange because they have so many mutations. So the immune cells attack with much more force,” Dr Cercek said.

https://www.euronews.com/health/2022/06/07/this-breakthrough-drug-trial-saw-cancer-vanish-in-every-patient

https://www.nejm.org/doi/full/10.1056/NEJMe2204282

PD-1 Blockade in Mismatch Repair–Deficient, Locally
Advanced Rectal Cancer

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2201445

morganism

  • Nilas ice
  • Posts: 2175
    • View Profile
  • Liked: 239
  • Likes Given: 149
Re: An Omega-3 That’s Poison for Cancer Tumors
« Reply #33 on: May 13, 2024, 11:14:36 PM »
(fascinating, the amount of deuterium heightened from cancer metabolism in the Krebs Cycle)

Scientists expose the atomic fingerprints of cancer cells

BOULDER, Colo. — We’re all made up of incredible tiny cells that work together to allow our bodies to function. Sometimes, however, cells can go rogue and start behaving in unhealthy ways that lead to serious diseases like cancer. Imagine if there was a way to simply look at the molecular makeup of cells and be able to tell whether they are operating normally or abnormally without any invasive testing. Well, scientists may have found a clever new method to do just that — uncovering the atomic fingerprints of cancer.

In a fascinating study published in the journal PNAS, researchers discovered that the levels of certain isotopes (different versions of the same element that have slightly varying weights) in the fatty acids of cells can reveal important clues about the cells’ inner metabolic workings. More specifically, the ratio of heavy hydrogen (deuterium) to normal hydrogen in fatty acids seems to act as a natural fingerprint, revealing whether cells are respiring normally or fermenting in an unhealthy way, as cancer cells do.

It all comes down to a crucial molecule called NADPH that acts as cells’ main supplier of energizing electrons for important biochemical reactions. The way cells produce NADPH depends on whether they are respiring by burning oxygen like a healthy cell or fermenting and rapidly proliferating like a cancerous cell. During normal respiration, cells produce more NADPH from an enzyme pathway that leaves a unique deuterium-enriched signature in the fatty acids those NADPH molecules help synthesize.

By contrast, cancer cells forced to ferment sugars for rapid growth rely more heavily on different NADPH-producing enzymes that create a deuterium-depleted pattern in the fatty acids they help generate. Simply put, by measuring the deuterium levels of extracted fatty acids, the researchers could tell whether the cells were healthy and respiring — or cancerous and fermenting.

“This study adds a whole new layer to medicine, giving us the chance to look at cancer at the atomic level,”

The scientists made this discovery by first running detailed experiments with ordinary baker’s yeast cells, a powerhouse model organism for studying cellular metabolism. Growing the yeast in special reactors and tightly controlling nutrient levels could force the yeast cells to either ferment sugar or burn an alternate food source like glycerol, mimicking the metabolisms of cancer and healthy cells, respectively.

When they carefully measured the deuterium/hydrogen ratios in the fatty acids extracted from yeast grown under fermenting versus respiring conditions, there was a massive difference – over 550 per million! Fermenting yeast had fat molecules depleted in deuterium, while the respiring yeast showed extreme deuterium enrichments. The degree of enrichment or depletion varied further with the rate of yeast growth, reflecting how cells reshuffle their NADPH-producing enzyme toolkit depending on metabolic demands.

To see if their yeast findings could translate to real life, the team also tested fatty acid deuterium levels in cancerous mouse liver cells and healthy mouse liver cells grown in lab dishes. Sure enough, the deuterium fingerprint matched that of the yeast experiments, with fatty acids from the fast-growing, fermenting cancer cells showing deuterium depletion compared to the normal, respiring liver cells.
(more)

https://studyfinds.org/atomic-fingerprints-cancer-cells/



 to track the primary cellular anabolic reductant, NADPH, are essential for understanding organismal health and disease. Here, we demonstrate that the variations in hydrogen stable isotope ratios of lipids are useful indicators of redox metabolism in the yeast Saccharomyces cerevisiae, a model microorganism for industry and studies of eukaryotic disease including cancer. Large differences in lipid hydrogen isotope ratios distinguish respiration and fermentation in yeast, reflecting shifts in the metabolic origins of NADPH. Changes in NADPH demand associated with cellular biochemical composition are also recorded in lipid hydrogen isotope ratios. These results provide promising tools to characterize eukaryotic metabolism, thus helping to elucidate the role of NADPH in health and disease.

 https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2310771121/- /DCSupplemental.Published May 6, 2024.MICROBIOLOGYENVIRONMENTAL SCIENCESLarge enrichments in fatty acid 2H/1H ratios distinguish respiration from aerobic fermentation in yeast

https://www.pnas.org/doi/epdf/10.1073/pnas.2310771121