>>15612253 (lb)
He aint mad. It is pasttime around here, bc it is fun triggering racists, religists, and other clowns who cannot rationalize or spread their prejudices and beLIEfs.
You love anons but hate niggers, yet many anons are niggers. And even more identify as such, as WWG1WGA.
Enjoy your dissonace and cortisol.
https://www.genengnews.com/topics/drug-discovery/therapeutics/immunotherapies/mrna-nanoparticles-restore-p53-function-improve-immunotherapy-response/
mRNA Nanoparticles Restore p53 Function, Improve Immunotherapy Response
February 10, 2022
Researchers at Massachusetts General Hospital (MGH) and Brigham and Women’s Hospital (BWH) have used mRNA nanoparticles to reprogram the tumor microenvironment of liver cancer and restore the function of the p53 master regulator gene, a tumor suppressor that is mutated in different cancer types. The researchers demonstrated that when used in combination with immune checkpoint blockade (ICB), the p53 mRNA nanoparticle technology—which is similar to that used in COVID-19 vaccines—not only induced suppression of tumor growth but also significantly increased antitumor immune responses in hepatocellular carcinoma (HCC) laboratory models.
“The reprogramming of the cellular and molecular components of the tumor microenvironment could be a transformative approach for treating HCC and other cancers,” said co-senior author Jinjun Shi, PhD, at the Center for Nanomedicine at BWH, who developed the platform with MGH liver cancer biologist and co-senior author Dan G. Duda, DMD, PhD. “By using this new approach, we’re targeting specific pathways in tumor cells with mRNA nanoparticles. These tiny particles provide the cells with the instructions to build proteins, which, in the case of HCC, delayed tumor growth and rendered the tumor more responsive to treatment with immunotherapy.”
The team described its development in Nature Communications, in a paper titled, “Combining p53 mRNA nanotherapy with immune checkpoint blockade reprograms the immune microenvironment for effective cancer therapy,” in which they concluded, “If successfully translated, the mRNA nanotherapy-based p53 restoration strategy could be transformative and impactful in cancer immunotherapy.”
HCC is the most prevalent form of liver cancer, characterized by a high mortality rate and “dismal prognosis” for patients, the authors wrote. Immune checkpoint blockers, a new class of drugs that enable the body’s immune system to recognize and attack cancer cells, have shown efficacy in treating HCC, but still, most patients do not benefit. To overcome this resistance to treatment, multiple strategies are being developed to improve ICBs by combining them with other existing therapies, such as anti-VEGF drugs and radiotherapy. However, even these approaches are expected to benefit only a small number of patients, creating an urgent need for new combination treatments. “Such combinations have been shown to improve anti-tumor efficacy in animal models and increase the survival of patients in clinical trials,” the team commented. “However, an increasing majority of HCC patients show no responses, and thus, new combinatorial strategies are still desperately needed.”
The tumor suppressor p53 is one of the most frequently mutated genes in a wide range of cancers, and is linked with tumorigenesis, tumor progression, resistance to anticancer therapy, and poor prognosis, the scientists said. “Beyond cell autonomous tumor-suppressive effects, increasing evidence indicates that p53 protein can also regulate the immune tumor microenvironment (TME) by modulating interactions of tumor cells with immune cells,” they noted. “Compelling evidence suggests that p53 dysfunction leads to immunosuppression and immune evasion.” The ability to restore p53 function might thus offer opportunities to reverse immunosuppression of the TME and improve the antitumor efficacy of ICB therapy.
Encouraged by the success of mRNA in COVID-19 vaccines, Shi decided to apply a modified form of the mRNA nanoparticle technology to target cancer cells. “The use of synthetic mRNA has attracted tremendous attention, as exemplified by the recent clinical approval of COVID-19 mRNA nano-vaccines and the clinical trials of a number of mRNA nanotherapeutics for diverse diseases including cancer,” the investigators noted. For the newly reported studies, Shi teamed up with Duda, whose MGH lab had already created sophisticated animal models to analyze the tumor microenvironment of liver tumors in response to immunotherapy.
The group developed and optimized an mRNA nanoparticle strategy to restore loss of function of p53, and reprogram the TME.
pt 1
>>15612342Their experiments and results highlighted evidence suggesting that p53 regulates the tumor microenvironment by modulating the interaction of cancer cells with immune cells as part of ICB therapy.
“In our previous work we had developed nanoparticles to target CXCR4—a chemokine receptor expressed by liver cancer cells—and selectively co-deliver drugs such as kinase inhibitors,” explained Duda. “We’ve now adapted this platform to use CXCR4 as a kind of zip code to selectively target the tumor with nanoparticles encapsulating therapeutic mRNAs. When we combined this nanomedicine with anti-programmed death receptor 1 (PD-1) antibodies, a standard immunotherapy for HCC patients, it induced global reprogramming of the tumor microenvironment and tumor response by restoring p53 expression.”
“This unique combinatorial strategy safely and effectively inhibits tumor growth in vivo, while prolonging survival and reducing ascites and metastases,” the scientists stated in their report. “…We find that combining CXCR4-targeted p53 mRNA nanoparticles with anti-PD-1 therapy effectively induces global reprogramming of cellular and molecular components of the immune TME. This effect results in improved antitumor effects compared to anti-PD-1 therapy or therapeutic p53 expression alone … Thus, combining p53 mRNA nanotherapy with ICB immunotherapy could become a transformative approach for the treatment of HCC and potentially other cancers involving p53 deficiency.”
The next step for the team is to transfer their research from animal models to patients in a clinical trial. “Scientists have struggled for decades to find an effective way to target the tumor suppressor pathways,” Shi noted. “Our proof-of-concept study is an exciting development that clearly shows that p53 mRNA nanoparticles in combination with ICB not only works, but also could make a big difference by reversing immunosuppression in HCC and potentially other cancers.”
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February 17, 2015
==Stealth Research
Is Biomedical Innovation Happening Outside the Peer-Reviewed Literature?==
John P. A. Ioannidis, MD, DSc1
Author Affiliations
JAMA. 2015;313(7):663-664. doi:10.1001/jama.2014.17662
https://jamanetwork.com/journals/jama/article-abstract/2110977
https://cen.acs.org/business/start-ups/mRNA-disrupt-drug-industry/96/i35
==Can mRNA disrupt the drug industry?
Messenger RNA technology promises to turn our bodies into medicine-making factories. But first Moderna—and a long list of old and new competitors—needs to overcome some major scientific challenges==
by Ryan Cross
September 3, 2018
https://www.nejm.org/doi/full/10.1056/NEJMc2200133
Protection against the Omicron Variant from Previous SARS-CoV-2 Infection
New England Journal of Medicine
February 9, 2022
DOI: 10.1056/NEJMc2200133
https://mobile.twitter.com/FamedCelebrity/status/1491533594983993347
William M Briggs
@FamedCelebrity
My friends have published a new paper which proves that He Who Controls The Data Creates The Science. https://mdpi.com/2073-4433/13/2/285…
Short thread of an email from one of the authors, showing how global warming can be created by statistics.
Whole thread below is quote.
In this paper…we looked at the various "temperature homogenization adjustments" that have been applied to the European temperature records in the widely used "Global Historical Climatology Network" (GHCN) dataset over the last 10 years.
The GHCN dataset is the main data source for thermometer records used by several of the groups calculating "global warming" - including NOAA, NASA Goddard Institute and the Japan Meteorological Agency.
Because these thermometer records typically are several decades to centuries long, they often are contaminated by "non-climatic biases" whenever the weather station undergoes a major change, such as being moved to a new location or a change in the type of instruments used.
In an attempt to try to correct for these non-climatic biases, NOAA, the group in charge of the GHCN dataset had been running a computer program to try and statistically identify "non-climatic jumps" in the records by comparing each station record to -
40 of its nearest neighbours. This process is called "temperature homogenization", and until now, most groups had been assuming the process was working correctly.
However, for this study, we analysed 10 years of different "homogenization adjustments" applied by NOAA -
to more than 800 European temperature records. We found that the adjustments NOAA was applying to each station record changed dramatically every time they re-ran their homogenization computer program! And they have been re-running this program almost every day since 2011.
We found that only 16% of the adjustments NOAA had been applying to the thermometer records were consistent from run to run.
Moreover, by compiling the "station history metadata" associated with each of the stations we analysed from the various national meteorological services and other scientific studies, we were able to compare the adjustments applied by NOAA to the documented station changes -
that were known to have occurred. We found that less than 20% of the adjustments NOAA had been applying corresponded to any event noted by the station observers - such as a change in instrumentation, station move, etc.
The findings of our study suggest that many of the "homogenization adjustments" that have been applied to the main thermometer records used for studying climate change over the last 10 years may have been spurious.
END QUOTE - BACK TO BRIGGS
I do not agree with homogenization. It fails for a number of reasons, too many to list here.
However, I have this handy series showing its faults, weaknesses, and cautions.
Gist: scientists are far too certain of themselves.
https://www.mdpi.com/2073-4433/13/2/285
how does that address the global human livestock plantation? where humans are sold, traded, slaved, and harvested
negras? negative.
slaves fighting slaves is as old as slavery. Believers only challenge each other, never the beLIEf shitstem and its puppeteers.
-so is emf transmission in specifc frequency ranges from devices, towers, bluetooth, IoT, IoB
-so is vaccination
-so is foreign sourced test swabs and DNA services
-so is weather manipulation
-so is media
-so is religion
-so is government
all instruments and applications of war and its instruments.
-so is election medling
-so is illegal surveillance
-so is blackmailingg buisness and politricker heads via their degenerate predelictions
-so is dual citizenship
-so is usury
-so is taxation.
etc
where is the human trafficking, money laundering, organ harvesting, and sex slaving, not to mention the trillions it generates?
Those shot callers look a little less melanated, eh? Your ignorant ass is hating on their food/slave supply. A category in which you too fall. But go ahead and ignore that part.
https://www.alumni.hbs.edu/stories/Pages/story-bulletin.aspx?num=3170
31 JAN 2014
BODY, HEAL THYSELF
Stéphane Bancel has taken Moderna Therapeutics from a one-man shop to a company that's poised to revolutionize the biotech world.
Re: Stefan Bancel (MBA 2000); By: Maureen Harmon
Topics: Health-Health Care and TreatmentInnovation-Technological InnovationStrategy-GeneralBusiness Ventures-Business StartupsCareer-GeneralScience-General
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BANCEL
Photo by Richard Howard
Throughout 2009 and 2010, Stéphane Bancel (MBA 2000) had received upward of 20 calls from biotech companies asking him to come aboard and lead the company. It made sense. He was a highly recruited CEO successfully running bioMérieux, a diagnostics company with 6,000 employees and sales reaching into the billions. Then one evening he got a call from Noubar Afeyan, managing partner and CEO of Flagship Ventures, a venture capital firm that started Moderna, asking Bancel to swing by the company's Boston office and take a look at the latest data coming in on their patented technology, messenger RNA (mRNA) Therapeutics.
The data that Bancel saw that evening were shocking. The numbers suggested Moderna had found an entirely new way to treat diseases—one that promised to change the medical world, resulting in cures for rare diseases and treatments for cancer. Even better, to a businessman like Bancel, the technology would be inexpensive to produce. Still, Bancel was incredulous. The numbers seemed too good to be true, and he was reluctant to leave a prestigious job to join a company with one employee and one patent. But then Afeyan said, "Stéphane, what if the data are correct?"
Bancel took a few weeks to weigh his options, and in mid-2011 he became president and founding CEO of Moderna. He feels certain that the company is producing something that could turn the biotech world—and the treatment of patients— on its head; and it all hinges on messenger RNA, or mRNA, the molecules responsible for transporting DNA code from a cell's nucleus to the ribosomes that create proteins. mRNA Therapeutics, as the company calls this new drug application, gives patients' cells the code they need to begin creating their own proteins and antibodies to fight disease.
This is how Bancel explains the process to his two young children: Think of your body as needing a recipe book, with each page detailing the directions to produce specific proteins. When a protein goes haywire—as might be the case with diabetes, when insulin needs to be produced to keep blood sugar levels in check—ideally a patient can be injected with Moderna's mRNA, which offers directions, or a specific recipe, to individual cells, which then use it to produce the protein or antibody needed to tackle the problem. In other words, mRNA Therapeutics offers a little help to the body so it can essentially heal itself.
It's all very exciting in theory, but moving a company from a one-man, one-patent startup to an organization that could change the face of therapy takes some business strategy. "We have a big sense of responsibility to make this happen," says Bancel, but "we are very well aware that [a breakthrough in] the biotech industry takes a lot of time; it takes a lot of money; it's complicated science."
And it takes a lot of people—from scientists to executives to board members. Bancel admits that people see the potential fairly quickly; the challenge will be to keep their attention along a lengthy path with plenty of bumps along the way, from the potential of failed trials to regulatory hurdles. He often reminds his team about their mission. "What excites us when we get out of bed is that we believe we have a chance to do something transformational for society and for patients."
pt1
In addition to guiding the Moderna team toward a long-term vision, Bancel is responsible for securing the funds to support the journey—ideally from investors who are on board with the mission, as well. He recalls one meeting with potential investors in Europe. He had made his case, but sensed apprehension in the body language of one investor. So Bancel turned to the man and said, "Even though we could use your money, do not invest." The potential investors were shocked. "It's because I know it's going to be a very long journey…I need investors who come along with us, who understand the potential but at the same time are comfortable with all of the things we're doing to reduce risk."
There's plenty of risk involved in biotech startups. The data might not pan out. The funds might not stream in, or all that "potential" might get caught up in the regulatory process. Investors and potential employees often worry about the red tape of regulatory agencies like the FDA, for example. Bancel explains, "Instead of being arrogant about it, instead of trying to put our heads in the sand and not deal with the issue, Noubar and I looked at each other, and we said, 'Who is the best person to help us through the challenges?'" The answer to that question was Peter Barton Hutt, former chief counsel for the FDA and an expert on food and drug law, so they recruited him to join the board.
Moderna is now winning over some very big supporters. In September of 2013, the company's academic cofounders, Kenneth Chien and Derrick Rossi, published a paper in the journal Nature Biotechnology that showed mRNA Therapeutics was capable of stimulating blood vessel growth, repairing damaged heart tissue, and helping a mouse through myocardial infarction.
pt2
In March of 2013, AstraZeneca offered the company $240 million for the development and exclusive use of the mRNA technology to treat cardiovascular, renal, and metabolic diseases as well as cancer. "It is one of the largest-ever initial payments in a pharmaceutical industry licensing deal that does not involve a drug already being tested in clinical trials," according to the New York Times. Then, in October, the government's Defense Advanced Research Projects Agency (DARPA) awarded Moderna $25 million to develop mRNA to combat infectious diseases and biological threats.
"What we're trying to do is not easy," says Bancel. "We were looking for people who were very experienced, who would be a good fit for the company, and we look for people who are a tiny bit crazy," he says. "You cannot claim you're trying to do something very special—that is very different—with people who can't think outside the box."
This, coming from a guy who did just that, setting aside a lucrative and promising career to take a chance on what could be the breakthrough that everyone is waiting for. "All my life I have been thinking about the next challenge," says Bancel when discussing his move to the company. "From HBS, I kept getting bigger and bigger jobs," including, he says, that big seat as bioMérieux CEO at the age of 33.
Now just 41, this man, who says he never wants to regret a thing, who was recruited to lead giant companies being traded on NASDAQ and NYSE, and who is willing to admit that he himself is a "tiny bit crazy," chose to lead a tiny biotech startup now in its third year—and it could be his biggest job yet.
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https://www.statnews.com/2016/09/13/moderna-therapeutics-biotech-mrna/
Ego, ambition, and turmoil: Inside one of biotech’s most secretive startups
Damian Garde
By Damian Garde Sept. 13, 2016