Heidelberg (Germany): Researchers from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and the Hebrew University in Jerusalem have discovered the cell of origin of mixed liver/biliary duct carcinomas, a rare type of liver cancer, in mice. Interleukin 6 is a pro-inflammatory immunological messenger that has been linked to cancer development (IL-6). The amount and size of tumours were reduced in mice after IL-6 was blocked.
The journal Hepatology published the study's findings.
Hepatocellular carcinoma, intrahepatic biliary duct carcinoma, and a hybrid form known as combined liver/biliary duct carcinoma (cHCC/CCA) are all included in the term "liver cancer." The cHCC/CCA cells display characteristics of both cancer types. This uncommon cHCC/CCA is thought to be extremely aggressive and responds terribly to current therapies.
A group led by Mathias Heikenwalder of the German Cancer Research Center and Eithan Galun of the Hebrew University in Jerusalem investigated the cellular basis of these tumours in order to find potential targets for novel therapies. The study subjects were genetically altered mice that had hepatocellular carcinoma and chronic liver inflammation at an earlier age, as well as later development of cHCC/CCA. The cHCC/CCA tumour cells in these animals largely shared the same molecular profile as the cHCC/CCA cells in humans. The German-Israeli team discovered that precursors of degenerate liver cells are where cHCC/CCA develops. Hepatocellular carcinoma, on the other hand, most likely results from damaged mature liver cells.
Genes involved in the pro-inflammatory interleukin 6 (IL-6) signalling pathway are highly active in cHCC/CCA cells. Ageing immune cells are the source of the IL-6 that activates this signalling pathway. Senescence, as scientists refer to the process of cell ageing, is characterised by the release of a wide variety of pro-inflammatory signalling molecules, the main one of which is IL-6.
Specific antibodies that block the action of IL-6 decreased the number and size of cHCC/CCA tumours in the mice. The growth of cHCC/CCA was also prevented by a substance that induces senescent cells to undergo programmed cell death, or apoptosis, which eliminates the source of IL-6.
Today, surgically removing the tumours is the most effective treatment for cHCC/CCA. It is only effective if the cancer is found very early on. According to Mathias Heikenwalder, one of the corresponding authors of the current study, "Blocking of IL-6 or agents that kill senescent IL-6-producing cells could now be further tested as promising treatment approaches against this type of cancer." He adds: "Growing evidence suggests that tumours that have been identified as hepatocellular carcinoma may also partially contain cHCC/CCA cells. This implies that some patients with hepatocellular cancer may also benefit from potential therapeutic strategies against cHCC/CCA."
At the DKFZ, more than 1,300 researchers look into how cancer arises, pinpoint cancer risk factors, and look for novel ways to prevent cancer. To more accurately identify tumours and successfully treat cancer patients, new techniques are being developed. The DKFZ's Cancer Information Service (KID) offers individualised responses to all questions on cancer to patients, interested citizens, and professionals. —ANI

Researchers from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and the Hebrew University in Jerusalem have discovered the cell of origin of mixed liver/biliary duct carcinomas, a rare type of liver cancer, in mice. Interleukin 6 is a pro-inflammatory immunological messenger that has been linked to cancer development (IL-6). The amount and size of tumours were reduced in mice after IL-6 was blocked.

A Rare Form Of Cancer Found In Mice

Washington: Biomedical engineers have demonstrated the most effective treatment for pancreatic cancer in mouse models ever recorded. While most mouse trials consider simply halting growth a success, the new treatment completely eliminated tumors in 80% of mice across several model types, including those considered the most difficult to treat. The approach combines traditional chemotherapy drugs with a new method for irradiating the tumor.
The approach combines traditional chemotherapy drugs with a new method for irradiating the tumor. Rather than delivering radiation from an external beam that travels through healthy tissue, the treatment implants radioactive iodine-131 directly into the tumor within a gel-like depot that protects healthy tissue and is absorbed by the body after the radiation fades away.
The results appear online on October 19 in the journal Nature Biomedical Engineering.
"We did a deep dive through over 1100 treatments across preclinical models and never found results where the tumors shrank away and disappeared like ours did," said Jeff Schaal, who conducted the research during his Ph.D. in the laboratory of Ashutosh Chilkoti, the Alan L. Kaganov Distinguished Professor of Biomedical Engineering at Duke. "When the rest of the literature is saying that what we're seeing doesn't happen, that's when we knew we had something extremely interesting."
Despite accounting for only 3.2% of all cancer cases, pancreatic cancer is the third leading cause of cancer-related death. It is very difficult to treat because its tumors tend to develop aggressive genetic mutations that make it resistant to many drugs, and it is typically diagnosed very late, when it has already spread to other sites in the body.
The current leading treatment combines chemotherapy, which keeps cells in a stage of reproduction vulnerable to radiation for longer periods of time, with a beam of radiation targeted at the tumor. This approach, however, is ineffective unless a certain threshold of radiation reaches the tumor. And despite recent advances in shaping and targeting radiation beams, that threshold is very difficult to reach without risking severe side effects.
Another method researchers have tried involves implanting a radioactive sample encased in titanium directly within the tumor. But because titanium blocks all radiation other than gamma rays, which travel far outside the tumor, it can only remain within the body for a short period of time before damage to surrounding tissue begins to defeat the purpose.&nbsp;
"There's just no good way to treat pancreatic cancer right now," said Schaal, who is now director of research at Cereius, Inc., a Durham, North Carolina biotechnology startup working to commercialize a targeted radionuclide therapy through a different technology scheme.
To skirt these issues, Schaal decided to try a similar implantation method using a substance made of elastin-like polypeptides (ELPs), which are synthetic chains of amino acids bonded together to form a gel-like substance with tailored properties. Because ELPs are a focus of the Chilkoti lab, he was able to work with colleagues to design a delivery system well-suited for the task.

The ELPs exist in a liquid state at room temperature but form a stable gel-like substance within the warmer human body. When injected into a tumor along with a radioactive element, the ELPs form a small depot encasing radioactive atoms. In this case, the researchers decided to use iodine-131, a radioactive isotope of iodine, because doctors have used it widely in medical treatments for decades and its biological effects are well understood.
The ELP depot encases the iodine-131 and prevents it from leaking out into the body. The iodine-131 emits beta radiation, which penetrates the biogel and deposits almost all its energy into the tumor without reaching the surrounding tissue. Over time, the ELP depot degrades into its constituent amino acids and is absorbed by the body -- but not before the iodine-131 has decayed into a harmless form of xenon.
"The beta radiation also improves the stability of the ELP biogel," Schaal said. "That helps the depot last longer and only break down after the radiation is spent."
In the new paper, Schaal and his collaborators in the Chilkoti laboratory tested the new treatment in concert with paclitaxel, a commonly used chemotherapy drug, to treat various mouse models of pancreatic cancer. They chose pancreatic cancer because of its infamy for being difficult to treat, hoping to show that their radioactive tumor implant creates synergistic effects with chemotherapy that relatively short-lived radiation beam therapy does not.
The researchers tested their approach on mice with cancers just under their skin created by several different mutations known to occur in pancreatic cancer. They also tested it on mice that had tumors within the pancreas, which is much more difficult to treat.
Overall, the tests saw a 100% response rate across all models, with the tumors being completely eliminated in three-quarters of the models about 80% of the time. The tests also revealed no immediately obvious side effects beyond what is caused by chemotherapy alone.
"We think the constant radiation allows the drugs to interact with its effects more strongly than external beam therapy allows," Schaal said. "That makes us think that this approach might actually work better than external beam therapy for many other cancers, too."
The approach, however, is still in its early preclinical stages and will not be available for human use anytime soon. The researchers say their next step is large animal trials, where they will need to show that the technique can be accurately done with the existing clinical tools and endoscopy techniques that doctors are already trained on. If successful, they look toward a Phase 1 clinical trial in humans.
"My lab has been working on developing new cancer treatments for close to 20 years, and this work is perhaps the most exciting we have done in terms of its potential impact, as late-stage pancreatic cancer is impossible to treat and is invariably fatal," Chilkoti said. "Pancreatic cancer patients deserve better treatment options than are currently available, and I am deeply committed to taking this all the way into the clinic." —ANI

Biomedical engineers have demonstrated the most effective treatment for pancreatic cancer in mouse models ever recorded. 

Study: Gel-Like, Radioactive Tumour Implant Obliterates Pancreatic Cancer In Mice

Sydney: Scientists at the University of Sydney found that a non-toxic technique can significantly reduce seed loss by keeping mice away from wheat crops. The study was published in the journal 'Nature Sustainability'. The method, created by researchers at the University of Sydney, has the potential to revolutionise the way crop loss caused by mice plague is managed. NSW Farmers estimated that the mice scourge could cost Australian crops $1 billion in damage in 2021. The research was led by PhD student Finn Parker, with co-authors Professor Peter Banks, Dr Catherine Price and Jenna Bytheway, from the Sydney Institute of Agriculture and School of Life and Environmental Sciences. The team estimated that mice successfully steal 63 per cent fewer wheat seeds, compared to untreated controls, if a wheat crop is sprayed with diluted wheat germ oil during and after sowing. The researchers found that if the wheat plot was also sprayed with the same solution before planting, then seed loss was reduced by an even better 74 per cent. They said this was because the mice had learned to ignore unrewarding wheat odour by the time the crop is planted. "We found we could reduce mice damage even during plague conditions simply by making it hard for mice to find their food, by camouflaging the seed odour. Because they're hungry, they can't spend all their time searching for food that's hard to find," Professor Banks said. "When the smell of the seed is everywhere, they'll just go and look for something else instead of being encouraged to dig. That's because mice are precise foragers that can smell seeds in the ground and dig exactly where a seed is, but they can't do that in this situation because everything smells like the seeds."  "This misinformation tactic could work well in other crop systems, indeed any animal that finds food by smell is potentially vulnerable to us manipulating that smell and undermining their ability to search." Mr Parker said the camouflage treatment could be an effective solution for wheat growers, given wheat's brief vulnerability. "The camouflage appeared to last until after the seeds germinated, which is the period of vulnerability when wheat needs to be protected," he said. "Most mouse damage occurs from when seeds are sown up to germination, just under two weeks later.: "Mice can't evolve resistance to the method either because it uses the same odour that mice rely on to find wheat seeds." The research was conducted in May 2021 on a farm 10 kms northwest of Pleasant Hills, New South Wales, where five treatments were tested across 60 plots. Two of the treatments involved the wheat germ oil solution. The other three treatments were controls, with plots covered in canola oil, trampled or left untreated. All control treatments performed similarly, receiving significantly more damage than treated plots. Wheat germ oil is a relatively inexpensive by-product of the milling process. The authors said their solution, which contains only wheat germ oil diluted in water, offers a sustainable, non-lethal alternative to pesticides and baits. "If people want to control mice but can't get numbers down low enough, our technique can be a potent alternative to pesticides or add value to existing methods," Dr Price said. —ANI

Scientists at the University of Sydney found that a non-toxic technique can significantly reduce seed loss by keeping mice 

Study discovers new method that lowers crop damage from mice, during plague

Washington: According to scientists, mice with a hereditary form of deafness have nearly normal neural activity in the auditory system for the first two weeks of life. Previous research suggests that this early auditory activity, prior to the onset of hearing, serves as a kind of training for the brain to process sound when hearing begins. The findings were published in PLOS Biology on June 27. According to some estimates, mutations in Gjb2 cause more than a quarter of all hereditary forms of hearing loss at birth in humans. The connexin 26 protein encoded by the gene belongs to the GAP junction protein family, which spans the tiny gap between cells to form a kind of tube that connects two cells to trade ions, metabolites, and other molecules that communicate or maintain equilibrium. This unexpected finding, according to investigators, suggests a molecular mechanism for the observation that people with this hereditary mutation respond well to cochlear implants. These electronic devices are designed to mimic sound conduction in the inner ear and can improve hearing in those with severe hearing loss. According to the National Institutes of Health, about 118,100 cochlear implants were implanted in adults and 65,000 in children between December 2019 and March 2021. The connexin 26 protein in the cochlea, the spiral-like structure in the inner ear, is highly enriched in supportive cells, which, as their name implies, provide structural and nutritional help to surrounding hair cells and auditory neurons. Previous studies have shown that, without connexin 26, the cochlea fails to develop its normal shape and is incapable of amplifying sound-induced vibrations necessary for efficient sound detection. Despite this disruption to the cochlear structure, this research shows the cochlea is still capable of producing the "spontaneous" activity needed to shape brain development. "Supportive cells are extremely important for tissues and organs," says neuroscientist Dwight Bergles, PhD, the Diana Sylvestre and Charles Homcy Professor at the Johns Hopkins University School of Medicine. "The new study shows how critical they are for training the auditory system and getting it ready to process sound." For the study, Bergles and Calvin Kersbergen, an M.D./Ph.D. candidate in Johns Hopkins' Medical Scientist Training Program, created a mouse model that lacked connexin 26 specifically in supportive cells in the cochlea. By using external electrodes to measure electrical responses in the auditory nerve in response to tones or clicks, they found that mice lacking connexin 26 only in supportive cells of the cochlea were, indeed, deaf, demonstrating the crucial role of these intercellular channels in hearing. However, Bergles and Kersbergen wondered if this change in supportive cells and cochlea shape would also disrupt spontaneous activity in younger mice, less than 2 weeks old before their ear canal opens. The researchers found that mice without connexin 26 still exhibit bursts of electrical activity in auditory neurons at nearly the same levels as young mice with intact connexin 26. Further investigation revealed that spontaneous activity in supportive cells was able to activate sensory hair cells in the inner ear, leading to normal neuronal activity in sound-processing areas of the brain. "Even in the absence of connexin 26, we still find robust spontaneous activity in the cochlea in these young mice," said Bergles. Bergles said there is evidence that the role of supportive cells in this early period is to "train" the auditory system to respond to sound at certain frequencies. Since the ear canal isn't open yet, supportive cells generate their own activity spontaneously to stimulate the mechanically sensitive hair cells in the fluid-filled cochlea. "It's as if the cochlea is producing its own 'sounds' at this stage of development," Bergles said. "This practice may help the auditory neurons and circuits in the brain mature before the ear canal opens." "It's like a baseball player in a batting cage, learning the basics of their swing and preparing to face the unpredictability of a real pitcher," said Bergles. Finally, the researchers found that spontaneous activity in supportive cells of deaf mice halts once the ear canal opens. At the same time, because the mice can't process sound, their auditory neurons actually increase their sensitivity to sound. This hypersensitivity to sound is similar to hyperacusis, in which normal sound levels can be painful. In humans, this hearing loss-induced hypersensitivity can also lead to constant ringing of the ears, called tinnitus. Bergles says the research also suggests a molecular mechanism for why people with this hereditary mutation who receive cochlear implants early on tend to do better than those who receive them later. "Spontaneous activity in supportive cells in the cochlea may provide the molecular evidence for empirical data showing better outcomes among people who have cochlear implants placed earlier in life," said Bergles. —ANI

According to scientists, mice with a hereditary form of deafness have nearly normal neural activity in the auditory system

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A Rare Form Of Cancer Found In Mice

Inam Ansari

The Hawk

Tag : Mice

A Rare Form Of Cancer Found In Mice

Inam Ansari

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