Category: Cancer

Categories : Cancer DermatologyTags :

Among Black Men, Study Finds Increased Mortality from Melanoma Diagnoses

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Photo by Nsey Benajah on Unsplash

Melanoma is often detected later in people with darker skin complexions – and the consequences can be devastating, according to the results of a Mayo Clinic study published in the Journal of Surgical Oncology.

While melanoma may be found less frequently in people with darker complexions than fair ones, this aggressive form of skin cancer, accounting for 75% of all skin-cancer-related deaths, can strike anyone. The study, which consisted of 492 597 patients with melanoma, suggests that added vigilance in early screening is particularly needed for Black men, whose cancers are often found at later stages, leading to worse outcomes compared to white patients or Black women.

“We compared non-Hispanic Black patients to white patients and saw striking differences in how patients presented with the disease,” says surgical oncologist Tina Hieken, MD, senior author of the study and a researcher at Mayo Clinic Comprehensive Cancer Center. “We saw more extremity melanoma, and more later-stage disease.”

Extremity melanoma refers to skin cancer that can develop on the arms, legs, hands and feet. Various factors, including social risk factors and biological components, could be at play, but further research is needed to help determine why these differences exist.

Revealing differences in sex-based immune response

The research found that Black female patients with melanoma fared better than Black male patients. Men tended to be older at diagnosis and more likely to have cancer that had spread to their lymph nodes compared to women. This translated to worse survival rates: the five-year survival for Black men with stage 3 melanoma was only 42% chance, compared to 71% for Black women.

Most research on melanoma hasn’t focused on how race and sex affect outcomes and hasn’t looked at the influence of race and ethnicity across all groups. Dr Hieken says the study highlights the need to understand these differences better, noting that this is the first large study to confirm that sex-based differences in melanoma outcomes exist within the non-Hispanic Black population.

“When we talk about later-stage melanoma patients who are female versus male in that non-Hispanic Black patient cohort who ended up doing worse, some biological things may be going on here that are interesting,” says Dr Hieken.

One theory centres on variations in immune response.

“Several immune signals suggest that women may respond better to some immunotherapies than males,” says Dr Hieken.

Researchers note that more studies focused on melanoma in a broader range of people, including more Black participants in clinical trials, is key to bridging this knowledge gap and potentially identifying more effective treatments.

Healthcare professionals should screen carefully

Dr Hieken notes that this study is a wake-up call for everyone battling to diagnose and cure melanoma, regardless of the patient’s sex or skin tone.

She emphasises that healthcare professionals should carefully examine areas like palms, soles and under fingernails, where melanoma might be more challenging to spot on darker skin.

“We can incorporate screening for skin lesions or lesions under the nails into the visit for patients as part of their regular checkups,” says Dr Hieken. “What we want to do is elevate care for our patients.”

Source: Mayo Clinic

Categories : Cancer GastrointestinalTags :

Intermittent Fasting Protects against Liver Inflammation and Liver Cancer

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Photo by jamie he

Fatty liver disease often leads to chronic liver inflammation and can even result in liver cancer. Scientists from the German Cancer Research Center (DKFZ) and the University of Tübingen have now shown in mice* that intermittent fasting on a five days on, two days off schedule can halt this development.

In mice with pre-existing liver inflammation, this fasting regime reduces the development of liver cancer . The researchers also identified two proteins in liver cells that are jointly responsible for the protective effect of fasting. An existing drug can partially mimic this effect.

The most common chronic liver condition is non-alcoholic fatty liver disease. If left untreated, it can lead to liver inflammation (metabolic dysfunction-associated steatohepatitis, MASH), liver cirrhosis and even liver cancer. Fatty liver disease is largely considered to be a direct consequence of obesity.

“The vicious circle of an unhealthy diet, obesity, liver inflammation and liver cancer is associated with major restrictions and suffering for those affected and also represents a considerable burden on healthcare systems,” says Mathias Heikenwälder, DKFZ and University of Tübingen. “We have therefore investigated whether simple dietary changes can specifically interrupt this fatal process.”

Intermittent fasting has already been shown in several studies to be an effective means of reducing weight and alleviating certain metabolic disorders. Heikenwälder’s team has now tested in mice whether this approach can also protect the liver from fatty degeneration and chronic inflammation. Their results are published in Cell Metabolism.

Resistance to liver inflammation is independent of calorie intake

The animals were fed with a high-sugar and high-fat diet corresponding to the typical Western diet. One group of mice had constant access to the food. As expected, these animals gained weight and body fat and developed chronic liver inflammation.

The mice in the other group were given nothing to eat on two days a week (5:2 intermittent fasting, or 5:2 IF for short), but were allowed to eat as much as they wished on the other days. Despite the high-calorie diet, these animals did not put on weight, showed fewer signs of liver disease and had lower levels of biomarkers that indicate liver damage. In short, they were resistant to the development of MASH.

Interestingly, resistance to the development of a fatty liver was independent of the total calorie intake, as the animals immediately made up for the lost rations after the end of the fasting periods.

When experimenting with different variants of intermittent fasting, it was found that several parameters determine protection against liver inflammation: The number and duration of fasting cycles play a role, as does the start of the fasting phase. A 5:2 dietary pattern works better than 6:1; 24-hour fasting phases better than 12-hour ones. A particularly unhealthy diet requires more frequent dieting cycles.

Heikenwälder’s team now wanted to find out the molecular background of the response to fasting. To this end, the researchers compared protein composition, metabolic pathways and gene activity in the liver of fasting and non-fasting mice. Two main players responsible for the protective fasting response emerged: the transcription factor PPARα and the enzyme PCK1. The two molecular players work together to increase the breakdown of fatty acids and gluconeogenesis and inhibit the build-up of fats.

“The fasting cycles lead to profound metabolic changes, which together act as beneficial detoxification mechanisms and help to combat MASH,” says Heikenwälder, summarizing the molecular details.

The fact that these correlations are not just a mouse phenomenon was shown when tissue samples from MASH patients were examined: Here, too, the researchers found the same molecular pattern with reduced PPAR α and PCK1. Are PPAR α and PCK1 actually responsible for the beneficial effects of fasting? When both proteins were genetically switched off simultaneously in the liver cells of the mice, intermittent fasting was unable to prevent either chronic inflammation or fibrosis.

The drug pemafibrate mimics the effects of PPARα in the cell. Can the substance also mimic the protective effect of fasting? The researchers investigated this question in mice. Pemafibrate induced some of the favourable metabolic changes that were observed with 5:2 fasting. However, it was only able to partially mimic the protective effects of fasting. “This is hardly surprising, as we can only influence one of the two key players with pemafibrate. Unfortunately, a drug that mimics the effects of PCK1 is not yet available,” explains Mathias Heikenwälder.

Intermittent fasting as liver therapy

While Heikenwälder and his team initially focused on the effects of intermittent fasting on MASH prevention, then investigated whether the 5:2 diet could also alleviate existing chronic liver inflammation.

To this end, the team examined mice that had developed MASH after months of being fed a high-sugar, high-fat diet. After a further four months of 5:2 intermittent fasting (on the same diet), these animals were compared with the non-fasting control group. The fasting mice had better blood values, less fatty liver and liver inflammation and above all: they developed less liver cancer and had fewer cancer foci in the liver.

“This shows us that 5:2 intermittent fasting has great potential – both in the prevention of MASH and liver cancer, as well as in the treatment of established chronic liver inflammation,” summarises principal investigator Heikenwälder. “The promising results justify studies in patients to find out whether intermittent fasting protects against chronic liver inflammation as well as in the mouse model.”

The 5:2 fasting regimen is popular. It is considered comparatively easy to integrate into everyday life, as the fasting days can be tailored to personal needs and no specific foods are prohibited. “Nevertheless, there will always be people who can’t stick to a strict diet in the long term,” says Heikenwälder. “That’s why we want to continue to investigate which combinations of drugs we can use to fully mimic the protective effects of fasting.”

Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Categories : Cancer General InterestTags :

Years after His Passing, Researcher’s Cancer Target Discovery Bears Fruit

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Some of the final work of a late University of Virginia School of Medicine scientist has opened the door for life-saving new treatments for solid cancer tumours, including breast cancer, lung cancer and melanoma.

Prior to his sudden death in 2016, John Herr, PhD, had been collaborating with Craig L. Slingluff Jr, MD, to investigate the possibility that a protein recently discovered at Herr’s lab could be a viable cancer treatment target.

Eight years of research has borne that idea out: Herr’s research into the SAS1B protein could lead to “broad and profound” new treatments for multiple cancers, many of which are very difficult to treat, Slingluff reports in a new scientific paper in the Journal for ImmunoTherapy of Cancer. Herr is listed as a senior author on the paper.

“John was very excited about this protein SAS1B to be a valuable new target on human cancers, and I am delighted that our findings together further support his hope to make such a difference,” said Slingluff, a surgical oncologist and translational immunologist at UVA Health and the UVA School of Medicine. “The work we published included work done by Dr Herr and his team over a period of years, as well as our subsequent work together; so, I am glad that the journal agreed with our request to include John as a senior author.”

Promising New Cancer Target

Herr’s lab was not originally focused on cancer – he was the head of UVA’s Center for Research in Contraceptive and Reproductive Health. In that role, he developed the first home fertility test for men, SpermCheck, which is available in pharmacies across the country. But his discoveries about the SAS1B protein found in developing eggs in women could pave the way for new cancer immunotherapies.

While SAS1B is found inside female reproductive cells called oocytes, it is also found on the surface of many different solid cancer cells, Slingluff’s new research verifies. Importantly, it did not appear on the surface of any of the other normal cells Slingluff’s laboratory tested. That suggests that doctors may be able to develop use antibody-based immunotherapy – such as antibody-drug conjugates or CAR T-cell therapy, a strength of UVA Health – to attack the cancer cells while sparing healthy tissue.

“Selectively targeting SAS1B has the potential to have broad and profound impact on the treatment, and therefore reduction in mortality, of multiple malignancies,” Slingluff and his colleagues write in their new paper.

While much more work needs to be done, the new findings are promising. If the approach is successful, it could be a big step forward in cancer care. Many solid-organ cancers are extremely difficult to treat, and patients often have few good treatment options, Slingluff notes.

“Immune therapy is revolutionising treatment of human cancers,” Slingluff said. “But some cancers have been particularly resistant to immune therapy because of the lack of good targets on those cancers. We hope that this work that John Herr started will bring new hope to patients with those cancers.”

Source: University of Virginia Health System

Categories : Cancer VaccinesTags :

mRNA Cancer Vaccine Unleashed on Glioblastomas in First Human Trial

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Photo by Anna Shvets

In a first-ever human clinical trial of four adult patients, an mRNA cancer vaccine developed at the University of Florida quickly reprogrammed the immune system to attack glioblastoma, the most aggressive and lethal brain tumour.

The results mirror those in 10 pet dog patients suffering from naturally occurring brain tumours whose owners approved of their participation, as they had no other treatment options, as well as results from preclinical mouse models. Next, the researchers will test the treatment in a Phase 1 paediatric clinical trial.

This breakthrough, published in Cell, represents a potential new way to recruit the immune system to fight notoriously treatment-resistant cancers using an iteration of mRNA technology and lipid nanoparticles, similar to COVID vaccines, but with two key differences: use of a patient’s own tumour cells to create a personalised vaccine, and a newly engineered complex delivery mechanism within the vaccine.

“Instead of us injecting single particles, we’re injecting clusters of particles that are wrapping around each other like onions, like a bag full of onions,” said senior author Elias Sayour, MD, PhD, a UF Health paediatric oncologist who pioneered the new vaccine, which like other immunotherapies attempts to “educate” the immune system that a tumour is foreign. “And the reason we’ve done that in the context of cancer is these clusters alert the immune system in a much more profound way than single particles would.”

Among the most impressive findings was how quickly the new method, delivered intravenously, spurred a vigorous immune-system response to reject the tumour, said Sayour, principal investigator of the RNA Engineering Laboratory within UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy and a UF Health Cancer Center and McKnight Brain Institute investigator who led the multi-institution research team.

“In less than 48 hours, we could see these tumours shifting from what we refer to as ‘cold’ – immune cold, very few immune cells, very silenced immune response – to ‘hot,’ very active immune response,” he said. “That was very surprising given how quick this happened, and what that told us is we were able to activate the early part of the immune system very rapidly against these cancers, and that’s critical to unlock the later effects of the immune response.”

Glioblastoma is among the most devastating diagnoses, with median survival around 15 months. Current standard of care involves surgery, radiation and some combination of chemotherapy.

The new publication is the culmination of promising translational results over seven years of studies, starting in preclinical mouse models and then in a clinical trial of 10 pet dogs that had spontaneously developed terminal brain cancer and had no other treatment options. That trial was conducted with owners’ consent in collaboration with the UF College of Veterinary Medicine. Dogs offer a naturally occurring model for malignant glioma because they are the only other species that develops spontaneous brain tumors with some frequency, said Sheila Carrera-Justiz, DVM., a veterinary neurologist at the UF College of Veterinary Medicine who is partnering with Sayour on the clinical trials. Gliomas in dogs are universally terminal, she said.

After treating pet dogs that had spontaneously developed brain cancer with personalised mRNA vaccines, Sayour’s team advanced the research to a small Food and Drug Administration-approved clinical trial designed to ensure safety and test feasibility before expanding to a larger trial.

In a cohort of four patients, RNA was extracted from each patient’s own surgically removed tumour, and then messenger RNA, or mRNA was amplified and wrapped in the newly designed high-tech packaging of biocompatible lipid nanoparticles, to make tumour cells “look” like a dangerous virus when reinjected into the bloodstream and prompt an immune-system response. The vaccine was personalised to each patient with a goal of getting the most out of their unique immune system.

“The demonstration that making an mRNA cancer vaccine in this fashion generates similar and strong responses across mice, pet dogs that have developed cancer spontaneously and human patients with brain cancer is a really important finding, because oftentimes we don’t know how well the preclinical studies in animals are going to translate into similar responses in patients,” said Duane Mitchell, M.D., PhD, director of the UF Clinical and Translational Science Institute and the UF Brain Tumor Immunotherapy Program and a co-author of the paper. “And while mRNA vaccines and therapeutics are certainly a hot topic since the COVID pandemic, this is a novel and unique way of delivering the mRNA to generate these really significant and rapid immune responses that we’re seeing across animals and humans.”

While too early in the trial to assess the clinical effects of the vaccine, the patients either lived disease-free longer than expected or survived longer than expected. The 10 pet dogs lived a median of 139 days, compared with a median survival of 30 to 60 days typical for dogs with the condition.

The next step will be an expanded Phase I clinical trial to include up to 24 adult and paediatric patients to validate the findings. Once an optimal and safe dose is confirmed, an estimated 25 children would participate in Phase 2, said Sayour.

Despite the promising results, the authors said one limitation is continued uncertainty about how best to harness the immune system while minimising the potential for adverse side effects.

“I am hopeful that this could be a new paradigm for how we treat patients, a new platform technology for how we can modulate the immune system,” Sayour said. “I am hopeful for how this could now synergise with other immunotherapies and perhaps unlock those immunotherapies. We showed in this paper that you actually can have synergy with other types of immunotherapies, so maybe now we can have a combination approach of immunotherapy.”

Source: University of Florida

Categories : CancerTags :

Activists and Patients March on Gauteng Health Department Demanding Radiation Treatment

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Nearly R800-million set aside for radiation treatment outsourcing has not been spent

Activists and patients marched on Tuesday in Johannesburg demanding radiation treatment for cancer. Photo: Silver Sibiya

By Silver Sibiya for GroundUp

Activists and cancer patients marched to the offices of the Gauteng department of health on Tuesday demanding that millions of rands allocated for radiation treatment for cancer patients be used.

SECTION27, Cancer Alliance and Treatment Action Campaign (TAC) called for the department to use R784-million set aside by the provincial treasury in March 2023 to outsource radiation treatment. They say not a single patient has received treatment through this intervention a year later.

In an open letter to health MEC Nomantu Nkomo-Ralehoko last week, Khanyisa Mapipa from SECTION27, Salomé Meyer from the Cancer Alliance and Ngqabutho Mpofu from TAC said that in March 2022, Cancer Alliance had compiled a detailed list of approximately 3000 patients who were awaiting radiation oncology treatment.

They said there were shortages of staff in the two radiation oncology centres in Gauteng, Steve Biko Academic Hospital and Charlotte Maxeke Johannesburg Academic Hospital. Charlotte Maxeke Hospital had only two operational machines compared to seven in 2020. Tenders for new equipment had been delayed and the backlog of patients was increasing, they said.

As a result, SECTION27 and Cancer Alliance had asked the provincial treasury to set aside R784-million to outsource radiation treatment. The money had been allocated in March 2023, but a year later, no service provider had been appointed.

“It has actually been four years since the matter was brought to the Department of Health,” said Mapipa on Tuesday. She said cancer patients were not getting the treatment they needed.

“We as Cancer Alliance and SECTION27 ran to Gauteng Treasury to ask them to allocate these funds. Gauteng Treasury responded and they gave this money, but this money is still sitting.”

Thato Moncho, who was diagnosed with breast cancer in September 2020, is one of the patients on the waiting list. She said she had faced many delays in her treatment. “I’ve had three recurrences of cancer and I need to have radiation six weeks after my surgery, which they failed to give me. I have pleaded with the MEC of Health and the Chief Executive Officer at Charlotte Maxeke to speed up the process so I can get my radiation but they failed.”

“I’m pleading: help us so we can get radiation to live a normal life with our family.”

Gauteng Department of Health spokesperson Motalatale Modiba said the department had received the memorandum and would respond to it. He acknowledged that there had been delays which he said were caused by tender processes.

“It is in our interest to ensure that we get to address the backlog of those that require treatment, and the department will formally respond to the concerns that have been raised.” He said a tender had been awarded.

“In May the process to treat patients will start in both hospitals.”

“The respective heads of oncology in Charlotte Maxeke and Steve Biko hospitals are busy with that process of onboarding.”

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Categories : CancerTags :

56% Stem Cell Donor Dropout Rate Puts Blood Cancer Patient Survival at Risk

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Twenty-five-year-old Amahle is a proud stem cell donor – despite her fear of needles. Photo: supplied.

South Africans in need of life-saving stem cell transplants face an uphill battle due to a high rate of donor attrition. While more than 30 000 South Africans registered as stem cell donors in 2023, a 43% increase year-on-year, more than half of matched donors changed their minds when they received the call.

Palesa Mokomele, Head of Community Engagement and Communications at DKMS Africa, says that donor attrition reduces the chances of survival for many patients. “Unlike other medical donations, such as donating blood, which take place immediately, stem cell donation is a multi-stage process, meaning that those who have registered may be contacted weeks, months, or even years after they have signed up if they are a possible match for a patient. “The uncertainty around whether and when they will be called on to donate therefore impacts donor availability.”

“If notified, they will be asked to undergo confirmatory typing to determine whether they are the best match for the patient and healthy enough to donate. It is usually at this point that they decide whether to proceed with the donation or not,” shares Mokomele.

“Finding a matching stem cell donor is already like searching for a needle in a haystack, so when they choose not to follow through, it further delays the process of locating suitable donors while also increasing wait times for transplants – putting patient survival at risk,” she points out.

To prevent this and help give patients a second chance at life as fast as possible, Mokomele urges those who have registered to regularly update their donor profile to reflect their current health status and availability. “Although it can take some time between registering and receiving the call that you’re a match, it is well worth the wait.”

Twenty-five-year-old Amahle, who recently answered the call, concurs, saying, “I couldn’t believe I was going to give another person a chance to live a healthy life.”

After receiving the news, she underwent confirmatory typing and a preliminary health check. She was also given a detailed briefing call on what to expect.

As with most cases, a Peripheral Stem Cell Donation was required, which is similar to a blood donation in 90% of cases. Blood is drawn and passes through a machine (apheresis machine) that collects the stem cells after which the rest of the blood is returned back into the body. This procedure does not require anaesthetic or admission to hospital and is normally completed within four to six hours. To help Amahle generate sufficient stem cell quantities, she was injected with a hormone-like substance called G-CSF in the lead up to the donation so her body can produce more stem cells for her genetic twin. G-CSF is safe and is a significant part of the process.

Finally, the big day arrived and although she was a ball of nerves (especially given her fear of needles), she pushed through. “I was strong. I knew I needed to continue because soon I was going to save a life.”

“We applaud Amahle’s selfless act. It is moments like these that remind us of the profound impact each individual can have on another’s life. At the same time, however, we are forced to acknowledge the sobering reality that 56% of registered donors drop out. With every registration, there is hope. But hope alone is not enough. Action is what truly makes a difference. We, therefore, urge South Africans between the ages of 17 and 55 who are in good health to not only register as a stem cell donor but to act when the call for donation comes,” concludes Mokomele.

Register today at https://www.dkms-africa.org/register-now.

Categories : Cancer UrogenitalTags :

Spotting the Aggressive Prostate Cancers among Urine Test Results

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Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health

Researchers have developed a new urine-based test that addresses a major problem in prostate cancer: how to separate the slow-growing form of the disease unlikely to cause harm from more aggressive cancer that needs immediate treatment.

The test, called MyProstateScore2.0, or MPS2, looks at 18 different genes linked to high-grade prostate cancer. In multiple tests using urine and tissue samples from men with prostate cancer, it successfully identified cancers classified as Gleason 3+4=7 or Grade Group 2 (GG2), or higher. These cancers are more likely to grow and spread compared to Gleason 6 or Grade Group 1 prostate cancers, which are unlikely to spread or cause other impact. More than one-third of prostate cancer diagnoses are this low-grade form. Gleason and Grade Group are both used to classify how aggressive prostate cancer is.

Results from the University of Michigan Rogel Cancer Center-led study are published in JAMA Oncology.

“Our standard test is lacking in terms of its ability to clearly pick out those who have significant cancer. Twenty years ago, we were looking for any kind of cancer. Now we realise that slow-growing cancer doesn’t need to be treated. All of a sudden, the game changed. We went from having to find any cancer to finding only significant cancer,” said co-senior study author John T. Wei, M.D., David A. Bloom Professor of Urology at Michigan Medicine.

Prostate-specific antigen, or PSA, remains the linchpin of prostate cancer detection. MPS2 improves upon a urine-based test developed by the same U-M team nearly a decade ago, following a landmark discovery of two genes that fuse to cause prostate cancer. The original MPS test, which is used today, looked at PSA, the gene fusion TMPRSS2::ERG, and another marker called PCA3.

“There was still an unmet need with the MyProstateScore test and other commercial tests currently available. They were detecting prostate cancer, but in general they were not doing as good a job in detecting high-grade or clinically significant prostate cancer. The impetus for this new test is to address this unmet need,” said co-senior author Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology. Chinnaiyan’s lab discovered the T2::ERG gene fusion and developed the initial MPS test.

“If you’re negative on this test, it’s almost certain that you don’t have aggressive prostate cancer,” said Chinnaiyan, S. P. Hicks Endowed Professor of Pathology and professor of urology at Michigan Medicine.

Moreover, MPS2 was more effective at helping patients avoid unnecessary biopsies. While 11% of unnecessary biopsies were avoided with PSA testing alone, MPS2 testing would avoid up to 41% of unnecessary biopsies.

“Four of 10 men who would have a negative biopsy will have a low risk MPS2 result and can confidently skip a biopsy. If a man has had a biopsy before, the test works even better,” Wei explained.

For example, a patient may get a prostate biopsy due to an elevated PSA, but no cancer is detected. The patient is followed over time and if his PSA inches up, he would typically need another biopsy.

“In those men who have had a biopsy before and are being considered for another biopsy, MPS2 will identify half of those whose repeat biopsy would be negative. Those are practical applications for patients out there. Nobody wants to say sign me up for another biopsy. We are always looking for alternatives and this is it,” Wei said.

Source: Michigan Medicine – University of Michigan

Categories : CancerTags :

Study Explains How Aspirin can Help Prevent Colorectal Cancer Development

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Photo by cottonbro studio

Studies have shown that long-term daily use of aspirin can help to prevent the development and progression of colorectal cancer, but the mechanisms involved have been unclear. New research has revealed that aspirin may exert these protective effects by boosting certain aspects of the body’s immune response against cancer cells. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

To investigate the effects of aspirin (a nonsteroidal anti-inflammatory drug) on colorectal cancer, investigators in Italy obtained tissue samples from 238 patients who underwent surgery for colorectal cancer in 2015–2019, 12% of whom were aspirin users. Patients were enrolled in the METACCRE section of the IMMUNOlogical microenvironment in the REctal Adenocarcinoma Treatment (IMMUNOREACT 8) multicenter observational study. The study was funded by the Associazione Italiana per la Ricerca sul Cancro (AIRC) and was mainly carried out at the University Hospital of Padova.

Compared with tissue samples from patients who did not use aspirin, samples from aspirin users showed less cancer spread to the lymph nodes and higher infiltration of lymphocytes into tumours. In analyses of colorectal cancer cells in the lab, exposing the cells to aspirin caused increased expression of a protein called CD80 on certain immune cells, which enhanced the capacity of the cells to alert other immune cells of the presence of tumour-associated proteins. Supporting this finding, the researchers found that in patients with rectal cancer, aspirin users had higher CD80 expression in healthy rectal tissue, suggesting a pro-immune surveillance effect of aspirin.

“Our study shows a complementary mechanism of cancer prevention or therapy with aspirin besides its classical drug mechanism involving inhibition of inflammation,” said principal investigator Marco Scarpa MD, PhD, of the University of Padova. “Aspirin is absorbed in the colon by passive diffusion to a significant degree. Its absorption is linear and depends on concentration along the bowel, and in the rectum, the concentration of orally administered aspirin can be much lower than in the rest of the colon. Thus, if we want to take advantage of its effects against colorectal cancer, we should think of how to guarantee that aspirin reaches the colorectal tract in adequate doses to be effective.” 

Source: Wiley

Categories : Cancer NeurologyTags :

New Drug Shows Promise for Treating Rare and Aggressive Gliomas

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MRI scan showing brain cancer. Credit: Michelle Monje, MD, PhD, Stanford University

An experimental drug may provide a new treatment option for some patients with rare incurable brain tumours, according to an analysis published in the Journal of Clinical Oncology.

Diffuse midline gliomas are diagnosed in about 800 people per year in the U.S., according to the Centers for Disease Control and Prevention.

A subset of particularly aggressive diffuse midline gliomas are caused by a H3 K27M mutation and the only effective treatment is radiation, as the location of the tumour in the brain makes surgery difficult. Even with radiation, relapse is virtually inevitable and more than 70% of patients with this subtype of brain tumour die from the cancer, according to the National Institutes of Health.

In the study, investigators analysed the results of five previous clinical trials testing the effectiveness of dordaviprone, an experimental drug which works by blocking a certain protein in tumours with the mutation.

The study included results from 50 patients (including four children) with H3 K27M–mutant diffuse midline gliomas and found that 30% of patients responded well to the drug. The most common side effect reported was fatigue, according to the study.

Now, the researchers are launching a trial at Northwestern Medicine hospitals to investigate the drug’s effectiveness in newly diagnosed patients.

Source: Northwestern University

Categories : Cancer NeurologyTags :

Epigenetic Changes Drive this Rare Malignant Paediatric Brain Tumour

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A healthy neuron. Credit: NIH

A new study published in Life Science Alliance revealed how aberrant epigenetic regulation contributes to the development of atypical teratoid/rhabdoid (AT/RT) tumours, which mainly affect young children. There is an urgent need for more research in this area as current treatment options are ineffective against these highly malignant tumours.

Most tumours take a long time to develop as harmful mutations gradually accumulate in cells’ DNA over time. AT/RT tumours are a rare exception, because the inactivation of one gene gives rise to this highly aggressive form of brain cancer.

AT/RT tumours are rare central nervous system embryonic tumours that predominantly affect infants and young children.

On average, 73 people are diagnosed with AT/RT in the USA each year. However, AT/RT is the most common central nervous system tumour in children under one years old and accounts for 40-50% of diagnoses in this age group. The prognosis for AT/RT patients is grim, with a postoperative median survival of only 11-24 months.

The collaborative study conducted by Tampere University and Tampere University Hospital examined how aberrant DNA methylation distorts cellular developmental trajectories and thereby contributes to the formation of AT/RT. DNA methylation is a normal process of controlling expression whereby methyl groups are added to the DNA strand, adding epigenetic information.

The new study showed that DNA methylation interferes with the activity of multiple regulators, which usually regulate the differentiation and maturation of central nervous system cells during brain development. Disrupted cell differentiation promotes the abnormal, uncontrolled proliferation of cells that eventually form a tumour.

The study also found several genes that regulate cell differentiation or inhibit tumour development and are silenced in AT/RT together with increased DNA methylation.

“These results will provide deeper insights into the development of AT/RTs and their malignancy. In the future, the results will help to accelerate the discovery of new treatments for this aggressive brain tumour,” says senior author Docent Kirsi Rautajoki from Tampere University.

Source: Tampere University