Researchers at the University of California, San Diego School of Medicine report that a protein called beta-catenin plays a critical, and previously unappreciated, role in promoting recovery of stricken hematopoietic stem cells after radiation exposure.
The findings, published in the May 1 issue of Genes and Development, provide a new understanding of how radiation impacts cellular and molecular processes, but perhaps more importantly, they suggest new possibilities for improving hematopoietic stem cell regeneration in the bone marrow following cancer radiation treatment.
Ionizing radiation exposure – accidental or deliberate – can be fatal due to widespread destruction of hematopoietic stem cells, the cells in the bone marrow that give rise to all blood cells. A number of cancer treatments involve irradiating malignancies, essentially destroying all exposed blood cells, followed by transplantation of replacement stem cells to rebuild blood stores. The effectiveness of these treatments depends upon how well the replacement hematopoietic stem cells do their job.
In their new paper, principal investigator Tannishtha Reya, PhD, professor in the department of pharmacology, and colleagues used mouse models to show that radiation exposure triggers activation of a fundamental cellular signaling pathway called Wnt in hematopoietic stem and progenitor cells.
“The Wnt pathway and its key mediator, beta catenin, are critical for embryonic development and establishment of the body plan,” said Reya, who also works at the Sanford Consortium for Regenerative Medicine. “In addition, the Wnt pathway is activated in stem cells from many tissues and is needed for their continued maintenance.”
The researchers found that mice deficient in beta-catenin lacked the ability to activate canonical Wnt signaling and suffered from impaired hematopoietic stem cell regeneration and bone marrow recovery after radiation. Specifically, mouse hematopoietic stem cells without beta-catenin could not suppress the production of oxidative stress molecules that damage cell structures. As a result, they could not recover effectively after radiation or chemotherapy.
“Our work shows that Wnt signaling is important in the mammalian hematopoietic system, and is critical for recovery from chemotherapy and radiation,” Reya said. “While these therapies can be life-saving, they take a heavy toll on the hematopoietic system from which the patient may not always recover.”
The findings have significant clinical implications.
“There are two major reasons why accelerating regeneration is important clinically,” said Reya. “One is that after cancer patients are irradiated and transplanted with stem cells, the rate and extent of recovery is often not sufficient to protect the patient from anemia or infections, which can be difficult to treat and sometimes deadly. Identifying signals that can boost regeneration after the bone marrow is severely damaged may help improve outcomes after transplantation.
“Second, doses of chemotherapy and radiation used to treat cancer are often limited by the collateral damage they cause to normal tissues. Although higher doses might kill more cancer cells more effectively, they can’t be used because they kill normal cells too. If we can improve and accelerate recovery, we might be able to use higher doses of radiation or chemotherapy and reduce the risk of cancer relapse.”
Reya said post-therapy hematopoietic stem cell regeneration could be accelerated by modulating the Wnt pathway, either by delivering additional Wnt proteins directly to patients or through drugs that activate the pathway. Further studies will be needed to determine if these approaches may be clinically useful to mitigate the damage caused by radiation and chemotherapy.
Cancer is really a brutal disease,I mean even if you get treatment for it,it still manages to destroy people lives.Patients gets to loose weight,hair falling out,anaemia,e.t.c when they receive this chemotherapy and radiography treatment,as if being diagnosed of cancer is not enough torture…The facts mentioned above will grant the patients a better chance to survive.Now they will have a positive mindset on getting better instead of worrying about side effects of the treatment only because of the commendable work the scientists managed to discover.A job well-done indeed.
What a astonishing discovery that was found. Many patients suffer from severe or terminal cancer every day, and not many make it. Stem cells are an astonishing discovery that was found, as many lives could be saved from this discovery.
As it was said in the article it was said that these cells are mainly found in the bone marrow, is it also true that stem cells are found in a babies umbilical cord, when they are born? If this is true, can the umbilical cords not be saved for each specific patient, and then be used when the patient does develop some sort of cancer or deficiency? This could also decrease the chances for anemia, because the patients OWN stem cells will be used.
This is a remarkable discovery, as this could lead to a brighter future for the generations to come.
What a remarkable discovery that was found. Many patients suffer from severe or terminal cancer every day, and not many make it. Stem cells are an astonishing discovery that was found, as many lives could be saved from this discovery.
As it was said in the article it was said that these cells are mainly found in the bone marrow, is it also true that stem cells are found in a babies umbilical cord, when they are born? If this is true, can the umbilical cords not be saved for each specific patient, and then be used when the patient does develop some sort of cancer or deficiency? This could also decrease the chances for anemia, because the patients OWN stem cells will be used.
This is a remarkable discovery, as this could lead to a brighter future for the generations to come.
Cancer treatment unfortunately involves chemotherapy and radiation which may irradicate cancer cells but also destroy healthy normal cells, especially hematopoietic stem cells which are in the bone marrow that give rise to all blood cells.
It is advised to administer post-therapy hematopoietic stem cell regeneration to patients to accelarate the Wnt pathway to stimulate red blood cell production.
Beta-Catenin protein plays a critical role in promoting recovery of hematopoietic stem cells after radiation helping the patient to recover faster and reducing the chance of infection, anaemia or a relapse.
I therefore agree that this research can have a positive impact on cancer patients lives as well as being beneficial to the medical field in the future.
Cancer is an illness which creates a lot of confusion in the minds of those it affects. The effects of chemotherapy and radiography don’t make it any easier. Weakness, hair loss and other physical changes make it very difficult for the patient to cope with what is going on and with what is going to follow.
It is important to take care of the fact that the patient is healthy enough to cope with such intense therapy. Patients who are weak have difficulty coping with radiation and chemotherapy.
This research is amazing, and I really felt that scientists are doing a remarkable job. Cancer has in some way or the other affected all of us. We all know of someone who has had cancer. Hence, such good news of progress to reduce or even eliminate side effects of Intense cancer therapy shows a ray of hope in thee hearts of us all.
The information above provides people with cancer a better chance to survive. This new development has caused a new turn in the medicine world. Doctors and Scientists can now improve the patients lives by means of chemotherapy. this is also good news for patients since now they can get cured with less side-effects and more health improvement.
The effects of chemotherapy and radiation therapy are different for every patient, because everyone is different. The amount of time it takes for the patient’s hair to grow back is different for each person. After my grandma got the necessary treatment for breast cancer it took her hair 3 months to grow back. Her sister also got the treatment a couple of years ago and it only took her hair 2 months to grow back. The effects of chemotherapy and radiation therapy depend on the type of medication and drugs that are used throughout the treatment. Some people lose a lot of weight during their treatment and others (like my grandma) don’t. The effects are different for each person, and everyone can only determine what the effects on them will be over time. “My cancer scare changed my life. I’m grateful for every new, healthy day I have. It has helped me prioritize my life,” – Olivia Newton-John
Cancer treatments such as chemo and radiation therapy are highly toxic to the human body which means they are usually not effective due to people being unable to recover or being negatively impacted by side effects caused thus therapies must be stopped before the cancer is eliminated.So to improve the rate at which a person recovers and how well a person recovers could improve the amount of survivors by a large number. With this research more people could have a better chance at eliminating the cancer as the rate of recovery will be higher ,which will also mean less suffering. This higher rate of recovery would mean that a person could endure more rounds of chemo therapy or higher doses of the chemo therapy.This research will be highly beneficial and should definitely be continued.
The treatment of Cancer is very strenuous and has many side effects such as hair loss and nausea. This new development in the medical division can create a huge positive impact on the way treatment for cancer is approached and done. With now knowing about this development in medicine, there is a way to help the patient feel more comfortable. When Wnt1 is administered, the process of recovery will be shortened and therefore if need be, more vigorous treatments will be done because the recovery will be quicker. The result of having more treatments given to the patient, the patient will hopefully recover from the disease in a shorter time and become cancer free. This new development can have a positive impact of many cancer patients lives and in the field of medicine
Wnt signaling was first identified for its role in carcinogenesis, which is the creation or production of cancer cells. Ever since its initial discovery, Wnt signaling has had an association with cancer. When Wnt1 was discovered, it was first identified as a proto-oncogene in a mouse model for breast cancer. The fact that Wnt1 is a homolog of Wg shows that it is involved in embryonic development, which often calls for rapid cell division and migration. Misregulation of these processes can cause unwanted cell growth and movement, which can lead to tumor development. So if the protein beta-catenin can be successfully administered to the patient and the Wnt pathways can be stimulated the redblood-cell producing bone marrow would be able to recover faster after the radiation and chemotherapy which will in turn allow for more frequent or higher doses of cancer treatment. This new development will be able to improve the effectiveness of cancer treatment and reduced the chance of a relapse. But not only will this knowledge be able to better cancer treatment but can be applied to other diseases that affect redblood-cell production like anaemia. Since cancer is a disease that almost affects everyone in some way I think this research is extraordinary.