Medical News Today: Cancer: Using copper to boost immunotherapy

An interdisciplinary group of scientists has successfully destroyed tumor cells in mice by using nano-sized copper compounds alongside immunotherapy. Importantly, the tumors did not return after the treatment ceased.

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Could copper compounds combined with immunotherapy help combat cancer?

According to the World Health Organization, cancer is the second leading cause of death worldwide — in 2018, it was responsible for approximately 9.6 million deaths.

Reducing behavioral or dietary risks associated with cancer is an important way of lowering the total number of cancer deaths; however, finding effective treatments is also crucial.

Doctors usually treat cancer with chemotherapy, but this often has significant side effects. For example, some chemotherapy medication can wipe out a person's white blood cells, leaving their immune system compromised and open to infection.

Although chemotherapy treatment can be successful, there is always a risk that a person's cancer might return.

Recent advances in cancer treatment include immunotherapy, which involves using a person's immune system to fight cancer cells. However, this does not always work or may only slow down the growth of cancer, so it cannot yet replace chemotherapy.

Copper nanoparticles

In the new study on mice, the scientists combined immunotherapy with copper-based nanoparticles. This combination treatment destroyed the tumor cells without the use of chemotherapy. Most importantly, however, the tumor cells did not return after treatment ceased.

The team of scientists — from KU Leuven in Belgium, the University of Bremen, the Leibniz Institute of Materials Engineering both in Germany, and the University of Ioannina in Greece — found that tumors in mice are sensitive to copper oxide nanoparticles.

Typically, these nanoparticles are toxic when inside an organism. The scientists found that by using iron oxide to create the nanoparticles, they could control which cells the nanoparticles destroyed, leaving healthy cells unaffected. They recently published their findings in the journal Angewandte Chemie International Edition.

Prof. Stefaan Soenen and Dr. Bella B. Manshian from the Department of Imaging and Pathology at KU Leuven worked together on the study. They explain how "any material that you create at a nanoscale has slightly different characteristics than its normal-sized counterpart." They continue:

"If we ingest metal oxides in large quantities, they can be dangerous, but at a nanoscale and at controlled, safe concentrations, they can actually be beneficial."

The scientists began by using only the nanoparticles to target the tumor cells. As expected, the cancer returned. However, the team discovered that the nanoparticles could work in conjunction with the mice's immune systems.

"We noticed that the copper compounds not only could kill the tumor cells directly, they also could assist those cells in the immune system that fight foreign substances, like tumors," said Dr. Manshian.

Blocking cancer's return

When the scientists combined the nanoparticles with immunotherapy, the tumor cells died and did not return.

To confirm the results, the scientists injected the mice with new tumor cells. The mice's immune systems immediately destroyed the new tumor cells.

The researchers believe that a combination of nanoparticles and immunotherapy could work as a vaccine for lung cancer and colon cancer, which were the two types of cancer the scientists studied.
However, they think that this technique could treat up to 60% percent of cancers, including breast cancer and ovarian cancer, that develop from the same gene mutation.

"As far as I'm aware, this is the first time that metal oxides [have been used] to efficiently fight cancer cells with long lasting immune effects in live models," Prof. Soenen says. "As a next step, we want to create other metal nanoparticles and identify which particles affect which types of cancer. This should result in a comprehensive database."

Results derived from animal testing do not necessarily work when it comes to humans, and to take the research further, the team intends to test the treatment on human tumor cells. If that is successful, they will conduct a clinical trial.
However, according to Prof. Soenen, there are still several hurdles along the way:

"Nanomedicine is on the rise in the United States and Asia, but Europe is lagging behind. It's a challenge to advance in this field because doctors and engineers often speak a different language. We need more interdisciplinary collaboration so that we can understand each other better and build upon each other's knowledge."

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Medical News Today: Does turmeric have anticancer properties?

A recent literature review investigates whether turmeric may be useful for treating cancer. The authors conclude that it might be but note that there are many challenges to overcome before it makes it to the clinic.

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Turmeric is loved the world over, but can it help fight cancer?

Turmeric is a member of the ginger family. Native to India and Southeast Asia, people have used turmeric root to flavor their food for thousands of years.

Historically, people associated turmeric with healing properties. Even now, some hail turmeric as a panacea for all ills. Recently, its popularity has surged, as evidenced by the recent turmeric latte fad. However, as with many things in life, the reality rarely matches the hype.

The chemical in turmeric that most interests medical researchers is a polyphenol called diferuloylmethane, which is more commonly called curcumin. Most of the research into turmeric's potential powers has focused on this chemical.

Turmeric as a healer?

Over the years, researchers have pitted curcumin against a number of symptoms and conditions, including inflammation, metabolic syndrome, arthritis, liver disease, obesity, and neurodegenerative diseases, with varying levels of success.

Above all, though, scientists have focused on cancer. According to the authors of the recent review, of the 12,595 papers that researchers published on curcumin between 1924 and 2018, 37% focus on cancer.

In the current review, which features in the journal Nutrients, the authors mainly focused on cell signaling pathways that play a role in cancer's growth and development and how turmeric might influence them.

Treatment for cancer has improved vastly over recent decades, but there is still a long path to tread before we can beat cancer. As the authors note, "the search for innovative and more effective drugs" is still vital work.

In their review, the scientists paid particular attention to research involving breast cancer, lung cancer, cancers of the blood, and cancers of the digestive system.

The authors conclude that "curcumin represents a promising candidate as an effective anticancer drug to be used alone or in combination with other drugs."

According to the review, curcumin can influence a wide range of molecules that play a role in cancer, including transcription factors, which are vital for DNA replication; growth factors; cytokines, which are important for cell signaling; and apoptotic proteins, which help control cell death.

Challenges remain

Alongside the discussions surrounding curcumin's molecular influence over cancer pathways, the authors also address the possible issues with using curcumin as a drug.

For instance, they explain that if a person takes curcumin orally — in a turmeric latte, for example — the body rapidly breaks it down into metabolites. As a result, any active ingredients are unlikely to reach the site of a tumor.

With this in mind, some researchers are trying to design ways of delivering curcumin into the body and protecting it from undergoing metabolization. For instance, researchers who encapsulated the chemical within a protein nanoparticle noted promising results in the laboratory and in rats.

Although scientists have published a great many papers on curcumin and cancer, there is a need for more work. Many of the studies in the current review are in vitro studies, which means that the researchers conducted them in laboratories using cells or tissues. Although this type of research is vital for understanding which interventions may or may not influence cancer, not all in vitro studies translate to humans.

Relatively few studies have tested turmeric's or curcumin's anticancer properties in humans, and the human studies that have taken place have been small-scale. However, aside from the difficulties and limited data, curcumin still has potential as an anticancer treatment.

Scientists are continuing to work on the problem. For instance, the authors mention two clinical trials that are underway, both of which aim to "evaluate the therapeutic effect of curcumin on the development of primary and metastatic breast cancer, as well as to estimate the risk of adverse events."

They also refer to other ongoing studies in humans that are evaluating curcumin as a treatment for prostate cancer, cervical cancer, and lung nodules, among other diseases.

The authors believe that curcumin belongs to "the most promising group of bioactive natural compounds, especially in the treatment of several cancer types." However, their praise for curcumin as an anticancer hero is tempered by the realities that their review has unearthed, and they end their paper on a low note:

"[C]urcumin is not immune from side effects, such as nausea, diarrhea, headache, and yellow stool. Moreover, it showed poor bioavailability due to the fact of low absorption, rapid metabolism, and systemic elimination that limit its efficacy in diseases treatment. Further studies and clinical trials in humans are needed to validate curcumin as an effective anticancer agent."

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Medical News Today: Using salt to fight cancer

Although scientists continually refine cancer treatments, there is still much room for improvement. A new study, carried out in mice, focuses on salt. The researchers have successfully used sodium chloride nanoparticles to destroy cancer cells.

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Injecting salt nanoparticles into mouse tumors restricted their growth significantly.

Over the decades, researchers have developed an ever-growing arsenal of drugs to combat cancer. However, many of these drugs are toxic, not only to cancer cells but to healthy tissue.

The hunt is still on to find more effective treatments with fewer negative consequences for the rest of the body.

Scientists — many from the University of Georgia, in Athens — are looking to sodium chloride, or salt, in nanoparticle form.

Sodium chloride is essential for life, but in the wrong place, it can cause cell death. To control this, ion channels on the plasma membranes that surround our cells prevent salt from entering.
Maintaining the right balance in the cell between sodium and chloride ions outside and potassium inside drives many processes that help support homeostasis — a consistent cellular environment.

Salt as a Trojan horse

The authors of the new study, published in the journal Advanced Materials, tested their theory that "Sodium chloride nanoparticles (SCNPs) can be exploited as a Trojan horse strategy to deliver ions into cells and disrupt the ion homeostasis."

SCNPs contain millions of sodium and chlorine atoms, but the ion channels responsible for keeping salt out do not recognize them in this form.
Consequently, SCNPs are free to enter the cell, and once inside, they dissolve, releasing sodium and chlorine ions that become trapped in the cell.

These ions disrupt cellular machinery and rupture the plasma membrane. As the cell membrane breaks open, the sodium and chlorine atoms are released. This, in turn, signals an immune response and inflammation.

Using a mouse model, the scientists tested their theory. They injected SCNPs into tumors and charted their growth. They compared the growth of these tumors with those of mice in a control group who had received the same quantity of sodium chloride in a solution, rather than as nanoparticles.

The team found that the SCNPs suppressed tumor growth by 66%, compared with the control group. Importantly, there were no signs that the SCNPs caused damage to any of the mice's organs.

The importance of safety

This method appears to be safe. As associate professor and lead author Jin Xie, Ph.D., explains: "After the treatment, the nanoparticles are reduced to salts, which are merged with the body's fluid system and cause no systematic or accumulative toxicity. No sign of systematic toxicity was observed with SCNPs injected at high doses."

Also, cancer cells seemed to be more susceptible to SCNPs than healthy cells. This, the authors believe, might be because cancer cells contain higher levels of sodium to begin with, making them more vulnerable to overload.

In recent years, many researchers have investigated whether various types of nanoparticles might be useful in medicine; yet very few have reached the clinic. As the authors of the study acknowledge, "Primary concerns are [the particles'] toxicity, slow clearance, and unpredictable long‐term impact to the hosts."

SCNPs, however, are different. The authors explain that "They are made of a benign material, and their toxicity is entirely hinged on the nanoparticle form."

A cancer vaccine?

In the second part of the study, the scientists investigated the effects of cancer cells that had already been killed by SCNPs. They injected these cells into mice and found that the animals were more resistant to developing new cancer; in other words, the cells acted as a vaccine.

This, they believe, is because when the SCNPs cause the cancer cells to die and burst open, they spark an immune response.

In a similar vein, the scientists carried out further studies in isolated tumor tissue. They injected SCNPs into primary tumors and measured the growth rates of secondary tumors.
The team found that the secondary tumors grew significantly slower than control secondary tumors, whose primary tumors had not been injected with SCNPs.

As skeptics often note, "Cancer has been cured thousands of times — in mice." With that said, all useful drugs must pass muster in animal research before scientists can test them in humans.

Xie is hopeful, saying that he expects SCNPs "to find wide applications in treatment of bladder, prostate, liver, and head and neck cancer."

Original Article

Medical News Today: How might bitter melon help treat cancer?

Bitter melon, or bitter gourd, has served as a traditional Indian remedy for centuries. Recently, bitter melon extract supplements have been gaining popularity as an alternative medication for diabetes. Now, new research in mice seems to suggest that bitter melon extract may help fight cancer.

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Research in mouse models finds that bitter melon may help treat cancer.

Bitter melon (Momordica charantia), also known as bitter gourd, is a "relative" of both cucumber and zucchini. It originated in the South Indian state of Kerala.

It later became more widespread, with China first importing the fruit in the 14th century. It then spread to regions of Africa and to the Caribbean.

Traditionally, bitter melon has helped treat many health concerns, and it has recently gained some popularity as a natural remedy against diabetes.

The fruit is also a staple of certain Asian cuisines, adding to local dishes' unique flavor through its specific bitterness.

Recently, Prof. Ratna Ray — from Saint Louis University in Missouri — and her colleagues made an intriguing find. In experiments using mouse models, bitter melon extract appeared to be effective in preventing cancer tumors from growing and spreading.

The researchers report their findings in a study paper that now appears in the journal Cell Communication and Signaling.

An ancient remedy coming to light again

Prof. Ray grew up in India, so she was familiar not just with the culinary qualities of bitter melon, but also with its alleged medicinal properties.

This made her curious as to whether or not the plant also harbored properties that would make it an effective aid to anticancer treatments.

She and her colleagues decided to put this to the test in a preliminary study by using bitter melon extract on various types of cancer cells — including breast, prostate, and head and neck cancer cells.

Laboratory tests showed that the extract stopped those cells from replicating, suggesting that it might be effective in preventing the spread of cancer.

In further experiments using mouse models, the researchers found that the plant extract was able to reduce the incidence of tongue cancer.

So, in their new study, Prof. Ray and team tried to find out what might give bitter melon compounds an edge against cancer cells.

This time, they used mouse models to study the mechanism through which bitter melon extract interacted with tumors of cancer of the mouth and tongue.

They saw that the extract interacted with molecules that allow glucose (simple sugar) and fat to travel around the body, in some cases "feeding" cancer cells and allowing them to thrive.

By interfering with those pathways, the bitter melon extract essentially stopped cancer tumors from growing, and it even led to the death of some of the cancer cells.

"All animal model studies that we've conducted are giving us similar results, an approximately 50% reduction in tumor growth," says Prof. Ray.

It remains unclear whether or not bitter melon would have the same effect in humans, but Prof. Ray and colleagues explain that, going forward, this is what they are aiming to find out.

"Our next step is to conduct a pilot study in [people with cancer] to see if bitter melon has clinical benefits and is a promising additional therapy to current treatments," she notes.

Prof. Ray seems convinced that the plant is, if nothing else, at least a positive contributor to personal health.

"Some people take an apple a day, and I'd eat a bitter melon a day. I enjoy the taste," she says.

"Natural products play a critical role in the discovery and development of numerous drugs for the treatment of various types of deadly diseases, including cancer. Therefore, the use of natural products as preventive medicine is becoming increasingly important."

Prof. Ratna Ray

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Medical News Today: Flu vaccines may shrink tumors and boost cancer treatment

Recent experiments in mouse models have shown that injecting an inactivated flu virus into cancer tumors makes them shrink and boosts the effectiveness of immunotherapy.

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Is the flu shot the next step in fighting cancer?

When it comes to cancer tumors, many factors influence whether or not they will respond to treatment. One of these is whether the tumors are "hot" or "cold." What does this mean?

In recent years, a new type of anticancer therapy has been gaining in popularity: immunotherapy. This form of therapy works by boosting the body's own immune response to cancer tumors.

However, for the therapy to have a higher chance of working, the tumors have to be "hot" tumors — that is, they must contain immune cells. If a tumor does not contain (enough) immune cells, or contains immunosuppressant cells, it is called a "cold" tumor.

One question that researchers have been trying hard to answer is: How do we turn cold tumors into hot tumors that will respond to immunotherapy?

A team of investigators from the Rush University Medical Center in Chicago, IL, may now have found an effective way of doing just that by using inactivated flu viruses — essentially, flu vaccines — in mouse model experiments.

The researchers explain their process, as well as their findings, in a study paper that now features in the journal PNAS.

New approach shrinks tumors in mice

The researchers got the idea for their new study by looking at data from the National Cancer Institute. The data indicated that people with lung cancer who had also been in the hospital with influenza-related lung infections tended to live longer than those with lung cancer who had not had a flu virus.

When they recreated this scenario in mouse models, the researchers confirmed that those with cancer tumors and influenza-related infections tended to live longer.

Going forward, the team wants "to understand how our strong immune responses against pathogens like influenza and their components could improve our much weaker immune response against some tumors," says senior study author Dr. Andrew Zloza.

"However," he adds, "there are many factors we do not understand about live infections, and this effect does not repeat in tumors where influenza infections do not naturally occur, like skin."

So, the researchers injected an inactivated influenza virus into melanoma tumors in mouse models.

They found that this "vaccine" turned tumors from cold to hot by increasing the concentration of dendritic cells in the tumors. These cells can stimulate an immune response, and indeed, they led to an increase in CD8+ T cells. These can recognize and destroy cancer cells.

As a result, the mice's melanoma tumors either grew at a slower rate or started shrinking.

Also, the researchers saw that delivering the flu vaccine into a melanoma tumor on one side of a mouse's body led to the reduction not just of the growth of the injected tumor, but also to the slower growth of another tumor, on a different side of the body, which they had not injected.

The researchers saw similar results when delivering the flu vaccine to tumors of metastatic triple-negative breast cancer in mouse models.

"Based on this result, we hope that in [humans], injecting one tumor with an influenza vaccine [will] lead to immune responses in their other tumors as well," says Dr. Zloza.

Flu shots might boost immunotherapy

"Our successes with a flu vaccine that we created made us wonder if seasonal flu vaccines that are already [Food and Drug Administration]-approved could be repurposed as treatments for cancer," Dr. Zloza adds.

"Since these have been used in millions of people and have already been shown to be safe, we thought using flu shots to treat cancer could be brought to patients quickly."

Dr. Andrew Zloza

The researchers therefore worked with specially engineered mouse models, into which they were able to transplant both tumors and immune cells from humans with lung cancer and metastatic melanoma.

Dr. Zloza and colleagues found that injecting these human-derived tumors with a regular, FDA-approved flu shot led them to shrink.

"Such [a] transplant allows us to utilize patient-grade drugs in a living system. This is as close as we can get to testing something ahead of a clinical trial," he explains.

The researchers also wanted to see if they could use flu shots as an adjuvant therapy — that is, as an aid to existing anticancer therapies.

So, in additional experiments, they delivered the flu shots alongside a form of immunotherapy that relies on immune checkpoint inhibitors. These are drugs that stimulate immune cells to mount an attack against cancer tumors.

In doing this, the researchers found two things. The first was that the flu vaccines were able to reduce tumor growth on their own, regardless of whether or not the targeted tumor responded to checkpoint inhibitor therapy.

The second was that when the tumor did respond to immunotherapy, the flu shot combination led to an even more pronounced reduction in tumor growth.

"These results propose that eventually both [people] who respond and who do not respond to other immunotherapies might benefit from the injection of influenza vaccines into the tumor, and it may increase the small proportion of patients that are now long-term responders to immunotherapies," says Dr. Zloza.

"Since humans and mice are about 95% genetically identical, the hope is that this approach will work in patients. The next step planned is to conduct clinical trials to test various factors," he concludes.

Original Article

Medical News Today: Through my eyes: Surviving cancer twice

"Helen, I'm so sorry to tell you that you have stage 4 ovarian cancer." I will never forget hearing those words.

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Cancer treatment was pretty grueling in the 1980s, and outcomes were a lot gloomier than they are today.

Nothing could ever prepare you for hearing your doctor say you have cancer. My life flashed before my eyes. I was in disbelief. How could I have cancer for the second time in my life?

I was only 48 years old at the time of my second cancer diagnosis, and I was already a survivor of a radical mastectomy due to breast cancer at the age of 32, just 2 years after I had given birth to my daughter, Julianne.

I received my diagnosis of breast cancer in 1972, and in those days, treatment was limited. The surgeon believed that a radical mastectomy of my right breast would give me the best outcome.

The doctor would prove to be correct, but I was no less devastated in the interim. I was the mother of three children, and instead of tending to my active children, I now needed to focus on my health and well-being.

However, I continued to live a blessed life. I was the wife of an Orthodox priest, a secretary, and a preschool Sunday school teacher. I was like any other mother, trying to prioritize my life. The difference being, if I got my priorities wrong, it could cost me my life.

Second cancer diagnosis

The second episode began almost 2 decades later when I woke up feeling very bloated and fatigued.

I didn't think much of it at first and thought I would feel better the next day. Yet the bloating continued, especially after eating, and I began feeling pressure in my lower abdomen. I decided it was time to contact the family physician.

The doctor ordered tests, but various X-rays, an ultrasound, and an MRI showed nothing. My doctor thought it was a case of gastritis and that I needed to rest and relax. However, 2 years later, my belly was now protruding, and I felt horrible pressure, so I asked my doctor for another test. This time they ordered a CT scan.

The CT scan showed something was not right, and I would need exploratory surgery to get more information. They found ovarian cancer tangled and webbed intricately through a large part of my lower anatomy.

The surgery lasted many hours, and my surgeon believed he had debulked 90% of the cancer. He also told me that I needed to undergo chemotherapy.

Cancer treatment was pretty grueling in the 1980s, and outcomes were a lot gloomier than they are today. I had already beaten cancer once, and the chance of surviving a second round seemed bleak.

I was offered a cocktail of Cisplatin, anthramycin, and Cytoxan as my best defense. Chemotherapy lasted 7 hours a day, and my side effects lasted even longer.

I was unable to complete my final round of chemo as my white blood count dropped too low. My oncologist thought the last round of chemo might have done more harm than good, so he discontinued the therapy one month short of 6 months.

The surgeon didn't mention a survival time frame to me, of course. He knew I had enough on my mind and didn't need to tell me that the consensus was that I had 6 months to live.

I guess God had a different plan.

Road to recovery

I was sitting at the dinner table, having no appetite, looking frail and gaunt, with numbness and tingling in both my hands and feet. I was so tired and thinking that I can't go on.

I didn't realize that I had said that out loud until I was snapped out of my daze by my daughter telling me: "You can't give up, you already lived longer than the doctor said you would."

I was shocked. I expected to be gone already but felt emboldened by the fact that I wasn't.

Like a boxer in the late rounds of a fight, I summoned energy I didn't know I had. I vowed to not only go another round but to win this fight. I did it once, and I'll do it again.

I got a second wind, but I needed something more, so I began exploring other avenues to find my cure. This wasn't an easy task in the days before internet searches, and it would take considerable effort.

In retrospect, I feel there were three things I did that helped in my healing and recovery. The surgery and chemotherapy were a big part of my treatment plan, but I knew I couldn't sit back and relax and let the doctors do all the work.

I went to church many nights, sometimes by myself. With my head bowed and body low, I asked God for forgiveness and strength, and to help rid me of any anger or resentment I had. As the wife of a priest, I received a lot of support, and people began praying for me all over the United States.

I also began juicing (long before the juicing craze began). I juiced mainly carrots, and once in a while, I would add garlic or an apple. I actually developed carotenosis, a condition that turns your skin orange — I drank so much carrot juice that I looked like a carrot!

The juice gave me valuable nutrition, and I found it easy to digest. The juicing seemed to provide me with energy, so I could continue to take care of my daily needs and responsibilities.

The third and possibly the most interesting approach that I discovered through a dear friend was a technique called "hands on therapy" by Janet Ziegler.

I met Janet through a friend, and during the introduction, I told her my name is Helen, and I have cancer. She turned towards me with a gentle, compassionate touch and told me, "You are Helen, and you had cancer."

She taught me a process called visualization. It was as if she retrained my mind into thinking the opposite of what I knew as fact.

Before falling asleep that night, I remember asking God to give me a sign of a rainbow that things would be alright. It was that evening I clearly saw a rainbow full of vibrant color. I woke up the following morning feeling refreshed and thankful. Shortly after that experience, I no longer believed I had cancer.

Counting my blessings

The most difficult time in my recovery process was that first year. Once I developed a routine of self-care, I continued to nurture myself and focus on my loved ones. I slept a lot and took many breaks.

Looking back, I really believe there was a time when I was in recovery that I stopped believing I had cancer. Perhaps I was in denial, or possibly my deep faith carried me through.

The days continued, turning into months and then years.

It's been 31 years since my battle with cancer. I'm now a widow, a grandmother five times, and a most appreciative multiple cancer survivor.

I can genuinely say, I have experienced God's loving grace in what my oncologist says is a medical miracle. I want to reach out and tell anyone going through a similar trauma that if I can do this, so can you.

It may seem like there's no end in sight, but if you keep fighting, you too can win. I want you to close your eyes and imagine yourself beating the odds just like me.

31 years cancer-free.

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